RAB7B: A Specialized Rab GTPase Regulating Retrograde Trafficking and Immune Cell Function

Introduction

RAB7B (UniProt: Q96AH8) is a small GTPase belonging to the Rab family, which constitutes the largest branch of the Ras superfamily with over 60 members in humans [yang-2004-rab7b-identification-abstract]. First identified by Cao and coworkers in 2004, RAB7B was initially characterized as a novel lysosome-associated GTPase selectively expressed in monocytes and monocyte-derived dendritic cells [yang-2004-rab7b-identification-abstract]. Despite sharing approximately 50-68% sequence similarity with its paralog RAB7A, subsequent research has established that RAB7B performs distinct cellular functions, primarily controlling retrograde transport from late endosomes to the trans-Golgi network (TGN) rather than the anterograde late endosomal maturation pathway regulated by RAB7A [progida-2010-endosome-tgn-abstract][bucci-2010-receptors-trafficking-fulltext].

RAB7B functions as a molecular switch that cycles between an active GTP-bound state and an inactive GDP-bound state. In its active form, RAB7B recruits effector proteins to regulate membrane trafficking, cytoskeletal reorganization, and signaling pathway modulation. The protein has emerged as a key regulator of immune cell function, controlling toll-like receptor (TLR) degradation in macrophages, modulating autophagy through interaction with Atg4B, and enabling dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton [wang-2007-tlr4-degradation-abstract][kjos-2017-autophagy-atg4b-abstract][vestre-2021-dc-migration-abstract].

Molecular Function as a Small GTPase

Like all Rab GTPases, RAB7B functions as a molecular switch regulated by guanine nucleotide exchange factors (GEFs) that promote GTP binding and GTPase-activating proteins (GAPs) that stimulate GTP hydrolysis to return the protein to its inactive GDP-bound state. The protein contains the characteristic P-loop NTPase domain, small GTPase domain, and Ras family domain that define the Rab family [horiuchi-2012-rab7-interaction-selectivity-abstract].

Structural analysis reveals that RAB7B and RAB7A, despite their sequence similarity, possess strikingly different electrostatic potentials and molecular interaction fields, particularly around the functionally critical switch regions that undergo conformational changes upon GTP binding [horiuchi-2012-rab7-interaction-selectivity-abstract]. These differences predict that RAB7A and RAB7B do not share binding partners including GEFs, GAPs, and effector proteins. Notably, computational clustering analysis places RAB7A in the 'Rab6' subcluster while RAB7B clusters with the 'Rab3' subfamily, indicating significant functional divergence despite their nomenclature suggesting isoform status [horiuchi-2012-rab7-interaction-selectivity-abstract].

A distinctive structural feature of RAB7B is the presence of a double-glycine motif at the beginning of switch 2, which is otherwise conserved in the Arf GTPase family but only found in RAB7B and RAB28 among Rab proteins. This motif may contribute to larger conformational changes upon nucleotide binding and potentially affects catalytic activity, though no crystal structure of RAB7B has yet been solved to directly assess this hypothesis.

The specific GEFs and GAPs that regulate RAB7B nucleotide cycling remain incompletely characterized. While RAB7A is activated by the Mon1-Ccz1 GEF complex and inactivated by GAPs such as TBC1D5 and Armus, whether these same regulators act on RAB7B is unclear given the predicted differences in protein-protein interaction surfaces.

Subcellular Localization and Dual Compartment Association

RAB7B exhibits a distinctive dual localization pattern that distinguishes it from RAB7A. Wild-type RAB7B localizes primarily to late endosomes and lysosomes, colocalizing with the lysosomal marker LAMP-1 [progida-2010-endosome-tgn-abstract][wang-2007-tlr4-degradation-abstract]. However, the constitutively active GTP-bound mutant (RAB7B Q67L) almost completely colocalizes with Golgi and TGN markers, demonstrating that the active form of the protein preferentially associates with the secretory pathway compartments [bucci-2010-receptors-trafficking-fulltext]. This contrasts with RAB7A, whose active Q67L mutant localizes exclusively to late endosomal and lysosomal compartments.

This dual localization pattern reflects RAB7B's functional role in mediating transport between these compartments. The protein is positioned at the interface of the late endocytic and secretory pathways, consistent with its role in retrograde transport from endosomes to the TGN [progida-2010-endosome-tgn-abstract].

In dendritic cells, RAB7B localization undergoes dynamic changes during maturation. The protein is highly expressed in immature dendritic cells and becomes strongly upregulated within approximately four hours of lipopolysaccharide (LPS) stimulation, correlating with the transition from antigen capture to migratory behavior [vestre-2021-dc-migration-abstract][borgdistefano-2015-trafficking-migration-fulltext].

Regulation of Retrograde Transport: Endosomes to TGN

The primary cellular function of RAB7B is the regulation of retrograde transport from late endosomes to the trans-Golgi network. This pathway is essential for the recycling of sorting receptors, lysosomal enzyme delivery, and the proper trafficking of various cargo molecules [progida-2010-endosome-tgn-abstract][progida-2012-sorting-receptors-abstract].

RAB7B regulates the trafficking of the cation-independent mannose-6-phosphate receptor (CI-MPR), a key sorting receptor that shuttles lysosomal hydrolases from the TGN to endosomes and must recycle back to the TGN to continue this delivery function [progida-2012-sorting-receptors-abstract]. Depletion of RAB7B or expression of dominant-negative mutants disrupts CI-MPR distribution, alters its synthesis and turnover rate, increases secretion of lysosomal enzymes, and impairs cathepsin D maturation [progida-2010-endosome-tgn-abstract][bucci-2010-receptors-trafficking-fulltext]. These phenotypes indicate that without proper retrograde transport, sorting receptors accumulate in endosomes while lysosomal enzyme delivery to lysosomes is compromised.

Beyond CI-MPR, RAB7B also controls the retrograde trafficking of sortilin, another sorting receptor involved in protein targeting to lysosomes [progida-2012-sorting-receptors-abstract]. Using retrieval assays, researchers demonstrated that RAB7B is required for transport of both CI-MPR and sortilin from endosomes to the TGN. Interestingly, RAB7B also affects carrier formation from the TGN; mutations or silencing of RAB7B reduce the tubulation of CI-MPR and sortilin-containing carriers from the trans-Golgi network, suggesting the protein plays roles in organizing vesicular transport in both directions [progida-2012-sorting-receptors-abstract].

The retrograde transport of bacterial toxins also depends on RAB7B. In cells depleted of RAB7B, internalized Shiga toxin fails to reach the Golgi apparatus, providing additional evidence that this GTPase controls endosome-to-TGN trafficking [progida-2010-endosome-tgn-abstract].

Importantly, RAB7B does not regulate the degradative pathway controlled by RAB7A. Degradation of epidermal growth factor (EGF) and its receptor (EGFR), which requires RAB7A-dependent transport to lysosomes, is unaffected by RAB7B silencing or overexpression [bucci-2010-receptors-trafficking-fulltext]. This functional separation demonstrates that despite their sequence similarity, RAB7A and RAB7B operate in parallel but distinct trafficking pathways.

Toll-Like Receptor Trafficking and Inflammatory Signaling

One of the most significant functional roles of RAB7B is the negative regulation of Toll-like receptor (TLR) signaling in immune cells. This function was first demonstrated for TLR4 in macrophages and subsequently extended to TLR9 [wang-2007-tlr4-degradation-abstract][yao-2009-tlr9-abstract].

In macrophages, RAB7B promotes the lysosomal degradation of TLR4 following LPS stimulation. RAB7B colocalizes with TLR4 in LAMP-1-positive lysosomal compartments and facilitates the translocation of TLR4 into lysosomes for degradation [wang-2007-tlr4-degradation-abstract]. Overexpression of RAB7B reduces LPS-induced production of pro-inflammatory cytokines including TNF-alpha, IL-6, nitric oxide, and IFN-beta, while suppressing activation of MAPK, NF-kappaB, and IRF3 signaling pathways. Conversely, silencing of RAB7B increases the overall level of TLR4, including its cell-surface pool, and causes accumulation of TLR4 in early endosomes, resulting in enhanced and prolonged inflammatory signaling [wang-2007-tlr4-degradation-abstract].

The mechanism involves RAB7B's role in retrograde transport. When RAB7B is depleted, TLR4 cannot efficiently recycle to the TGN and is forced to remain in the early endocytic route longer, which may increase signaling duration [bucci-2010-receptors-trafficking-fulltext]. This model integrates RAB7B's trafficking function with its effects on receptor signaling.

Similar findings were reported for TLR9. RAB7B localizes with TLR9 in lysosomal compartments following TLR9 activation and promotes TLR9 degradation, thereby suppressing TLR9-initiated production of TNF-alpha, IL-6, and IFN-beta and impairing downstream activation of MAPKs and NF-kappaB pathways [yao-2009-tlr9-abstract].

These findings establish RAB7B as an important negative regulator of innate immune responses, providing a mechanism for terminating TLR signaling and preventing excessive inflammation.

Modulation of Autophagy via Atg4B Interaction

RAB7B negatively regulates autophagy through a direct interaction with the cysteine protease Atg4B [kjos-2017-autophagy-atg4b-abstract]. Atg4B processes pro-LC3 to generate LC3-I, which becomes lipidated to LC3-II on autophagosomal membranes. The enzyme also mediates delipidation of LC3-II, thereby regulating autophagosome size and turnover.

Atg4B binds preferentially to the active GTP-bound form of RAB7B, and the two proteins colocalize on vesicle membranes with a dynamic interaction averaging approximately 122 seconds [kjos-2017-autophagy-atg4b-abstract]. Through this interaction, RAB7B modulates Atg4B's delipidation activity. Depletion of RAB7B reduces Atg4B delipidation activity, leading to increased LC3-II accumulation and enhanced autophagic flux.

Cells lacking RAB7B display characteristic autophagy phenotypes including increased autophagosomal size (approximately 16% enlargement measured by electron microscopy), elevated LC3-II levels (approximately twofold under both basal and starvation conditions), and enhanced macroautophagic sequestration and cargo degradation [kjos-2017-autophagy-atg4b-abstract]. Importantly, autophagosome-lysosome fusion and acidification remain intact, indicating that RAB7B specifically regulates autophagosome expansion rather than maturation or degradation steps.

This function represents a novel role for RAB7B beyond its established trafficking functions and demonstrates that the protein participates in coordinating cellular degradation pathways.

Actomyosin Regulation and Cell Migration

Beyond membrane trafficking, RAB7B plays an unexpected role in regulating the actin cytoskeleton and cell migration. This function was discovered through identification of myosin II as a RAB7B interaction partner in yeast two-hybrid screens [borgdistefano-2015-trafficking-migration-fulltext].

RAB7B influences the RhoA-ROCK-myosin light chain phosphorylation signaling axis that controls actomyosin contractility [borgdistefano-2015-trafficking-migration-fulltext]. Depletion of RAB7B results in reduced stress fiber formation, decreased cell spreading on fibronectin, and substantially impaired cell migration and polarization responses to wounding. RAB7B transport is dependent on myosin II activity, indicating bidirectional functional coupling between the GTPase and the motor protein.

The most detailed characterization of RAB7B's role in cell migration comes from studies in dendritic cells [vestre-2021-dc-migration-abstract]. Mature dendritic cells normally accelerate their migration speed from approximately 4.8 micrometers per minute (immature) to 8.4 micrometers per minute (mature), but RAB7B-knockout cells fail to achieve this speed increase. RAB7B-deficient mature dendritic cells retain immature characteristics including sustained macropinocytosis, reduced directional persistence, and altered actin distribution favoring the cell front rather than rear.

The mechanistic basis involves RAB7B's interaction with the lysosomal calcium channel TRPML1 (also known as MCOLN1) [vestre-2021-dc-migration-abstract]. RAB7B physically bridges TRPML1 to myosin II, enabling local calcium-dependent activation of myosin II at the cell rear, which is essential for generating the contractile forces that propel cell movement. In the absence of RAB7B, myosin light chain phosphorylation is reduced by approximately 50%, and nuclear translocation of TFEB (transcription factor EB), the master regulator of lysosomal biogenesis, is suppressed.

Critically, artificial activation of TRPML1 with the agonist ML-SA1 cannot restore myosin II phosphorylation in RAB7B-knockout cells, demonstrating that physical recruitment of myosin II to lysosomes—not merely calcium availability—is required for this signaling pathway [vestre-2021-dc-migration-abstract]. These findings establish RAB7B as the missing physical link between lysosomes and the actomyosin cytoskeleton, enabling control of immune cell migration through lysosomal signaling.

Expression Pattern and Tissue Distribution

RAB7B exhibits a notably restricted expression pattern compared to RAB7A. The protein is selectively expressed in monocytes (CD14+ cells), monocyte-derived immature dendritic cells, and promyeloid/monocytic leukemia cell lines such as HL-60 and NB4 [yang-2004-rab7b-identification-abstract]. In peripheral blood, RAB7B is specifically detected in CD14+ cells but not in CD4+, CD8+, CD19+, or CD56+ cells, suggesting it may serve as a monocytic cell marker.

Analysis of broader tissue distribution reveals that RAB7B mRNA is expressed in human heart, placenta, lung, skeletal muscle, and peripheral blood leukocytes [yang-2004-rab7b-identification-abstract]. According to the Human Protein Atlas, RAB7B shows tissue-enhanced expression in skin with the highest normalized transcripts per million (nTPM of 49.2), followed by esophagus, gallbladder, vagina, and cervix. In the brain, RAB7B transcripts localize to white matter and myelinating cells, specifically in differentiated oligodendroglial lineage cells [fukushima-2023-oligodendrocyte-abstract].

RAB7B expression is dynamically regulated during immune cell differentiation and activation. In dendritic cells, RAB7B is strongly upregulated approximately four hours after LPS stimulation before gradually declining as cells fully mature [borgdistefano-2015-trafficking-migration-fulltext]. In monocytes, LPS treatment upregulates RAB7B expression. In acute promyelocytic leukemia cell lines, RAB7B expression increases upon phorbol myristate acetate (PMA)-induced monocytic differentiation [yang-2004-rab7b-identification-abstract].

Roles in Cell Differentiation

RAB7B participates in hematopoietic cell differentiation beyond monocyte/dendritic cell development. The protein promotes megakaryocytic differentiation by enhancing IL-6 production through NF-kappaB activation [he-2011-megakaryocyte-abstract]. RAB7B strengthens PMA-induced differentiation of K562 leukemia cells toward megakaryocytes, as evidenced by morphological alterations, increased fibronectin-specific adhesion, polyploidy formation, and expression of megakaryocytic markers such as CD41a.

The mechanism involves RAB7B-mediated enhancement of IL-6 secretion, which activates STAT3 (signal transducer and activator of transcription 3). Activated STAT3 then associates with the transcription factor GATA-1 to upregulate megakaryocytic differentiation genes [he-2011-megakaryocyte-abstract]. Both the GTP-bound status and lysosomal localization of RAB7B are required for this function. Blocking NF-kappaB, IL-6, or the IL-6 signaling receptor gp130 prevents RAB7B's differentiating effects.

In the central nervous system, RAB7B and RAB7A play opposing roles in oligodendrocyte differentiation [fukushima-2023-oligodendrocyte-abstract]. While RAB7A promotes oligodendroglial cell morphological differentiation, RAB7B inhibits this process. Knockdown of RAB7B in FBD-102b oligodendrocyte precursor cells promotes differentiation, and importantly, can recover differentiation defects caused by tunicamycin-induced endoplasmic reticulum stress that mimics the molecular pathology of hereditary hypomyelinating disorders such as Pelizaeus-Merzbacher disease [fukushima-2023-oligodendrocyte-abstract].

Comparison with RAB7A: Distinct Paralogs with Different Functions

Although RAB7B was initially characterized as a potential isoform of RAB7A based on sequence similarity, extensive functional characterization has established that these proteins perform distinct cellular roles and should be considered functionally divergent paralogs rather than isoforms.

RAB7A is a ubiquitously expressed protein that regulates early-to-late endosomal maturation and transport from late endosomes to lysosomes, playing essential roles in degradation of internalized cargo including EGFR [bucci-2010-receptors-trafficking-fulltext]. RAB7A also participates in autophagosome-lysosome fusion, mitophagy, and interacts with well-characterized effectors including RILP (Rab-interacting lysosomal protein) and the retromer complex via VPS35 [bucci-2010-receptors-trafficking-fulltext].

In contrast, RAB7B controls retrograde transport from endosomes to the TGN, does not affect EGFR degradation, and has identified interactions with myosin II, Atg4B, and TRPML1 that are not shared with RAB7A [progida-2010-endosome-tgn-abstract][kjos-2017-autophagy-atg4b-abstract][vestre-2021-dc-migration-abstract]. The expression pattern also differs dramatically, with RAB7B showing cell-type restricted expression primarily in myeloid cells while RAB7A is broadly expressed.

Bioinformatic analysis of electrostatic potentials and molecular interaction fields around the switch regions predicts that RAB7A and RAB7B do not share GEFs, GAPs, or effector proteins [horiuchi-2012-rab7-interaction-selectivity-abstract]. Disease associations also differ: mutations in RAB7A cause Charcot-Marie-Tooth disease type 2B, while no diseases have been associated with RAB7B mutations, possibly suggesting that RAB7B mutations are embryonically lethal or produce subtle phenotypes [horiuchi-2012-rab7-interaction-selectivity-abstract].

Post-Translational Modifications and Membrane Association

RAB7B, like other Rab GTPases, undergoes post-translational modifications that are essential for its membrane association and function. The protein is 199 amino acids in length and terminates in a di-cysteine (CC) motif at positions 198-199 [UniProt-Q96AH8]. Both C-terminal cysteine residues are modified by the attachment of S-geranylgeranyl groups, a lipid modification catalyzed by Rab geranylgeranyltransferase (RabGGTase or GGTase-II) in conjunction with Rab escort protein (REP) [UniProt-Q96AH8].

This double geranylgeranylation is characteristic of Rab proteins and distinguishes their prenylation from Ras family proteins, which typically undergo single farnesylation or geranylgeranylation at CAAX motifs. The dual lipid modification enables stable association of RAB7B with target membranes and is required for proper localization and function. The GDP-bound form associates with membranes through lipid-lipid interactions, while the GTP-bound form additionally recruits effector proteins.

Beyond prenylation, RAB7B is phosphorylated at serine 186, though the functional significance of this modification and the kinase(s) responsible remain to be characterized [UniProt-Q96AH8]. Phosphorylation may regulate RAB7B activity, localization, or interactions with binding partners.

The protein contains the canonical Rab GTPase structural elements including Switch 1 (residues 28-41) and Switch 2 (residues 67-82) regions that undergo conformational changes upon GTP binding and mediate interactions with regulatory and effector proteins. Multiple GTP-binding sites are distributed throughout the protein at positions 15-22, 34-40, 63-67, 124-127, and 154-155 [UniProt-Q96AH8].

Neuroprotection in Ischemic Stroke

RAB7B's role as a negative regulator of TLR4 signaling has been extended to neuroprotection in cerebral ischemia. In a rat model of transient middle cerebral artery occlusion (tMCAO), RAB7B expression is upregulated in the brain following stroke [qi-2019-stroke-neuroprotection-abstract]. Functional studies demonstrated that overexpression of RAB7B through DNA transfection reduced cerebral infarction volume and improved neurological outcomes.

The neuroprotective mechanism involves suppression of the TLR4-NF-kappaB inflammatory pathway that contributes to ischemia-induced brain damage [qi-2019-stroke-neuroprotection-abstract]. RAB7B overexpression suppressed expression of both TLR4 and NF-kappaB p65, inhibited activation of NF-kappaB p65, and reduced production of pro-inflammatory cytokines including TNF-alpha, IFN-gamma, IL-1beta, and IL-6 in the ischemic brain tissue.

These findings are consistent with RAB7B's established role in promoting TLR4 degradation in macrophages and suggest that RAB7B may represent a therapeutic target for reducing neuroinflammation following stroke. The upregulation of RAB7B following ischemia may represent an endogenous protective response to limit inflammatory damage, and augmentation of this response through RAB7B overexpression provides additional neuroprotection.

Additional Cellular Contexts

Beyond its primary functions in trafficking and immune regulation, RAB7B has been implicated in pathogen response. The protein is recruited to phagosomes containing bacterial pathogens including Staphylococcus aureus and Mycobacterium tuberculosis [UniProt-Q96AH8], suggesting involvement in the phagosomal maturation pathway or regulation of antimicrobial responses.

The relationship between RAB7B and the retromer complex, a key mediator of endosome-to-TGN transport, remains incompletely defined. While RAB7A directly interacts with the VPS35 subunit of retromer and recruits the complex to endosomal membranes, whether RAB7B shares this interaction is uncertain given the predicted differences in their protein-protein interaction surfaces. The functional requirement for RAB7B in retrograde transport may involve distinct effector mechanisms or partially overlapping pathways with retromer-mediated retrieval.

Open Questions

Several important questions about RAB7B remain to be addressed:

1. Structural characterization: No crystal structure of RAB7B has been solved. Structural determination would clarify the impact of the double-glycine motif in switch 2 on nucleotide binding and hydrolysis, and would enable structure-based comparison with RAB7A to understand their functional divergence.

2. GEF and GAP identification: The specific regulatory proteins that control RAB7B nucleotide cycling remain unknown. Identifying RAB7B-specific GEFs and GAPs would illuminate how this GTPase is spatially and temporally regulated.

3. Complete effector repertoire: Beyond myosin II, Atg4B, and TRPML1, additional RAB7B effectors likely remain to be discovered. Systematic interactome studies would provide a comprehensive view of RAB7B's functional networks.

4. Role in disease: Despite its restricted expression and roles in immune cell function, no human diseases have been directly attributed to RAB7B dysfunction. Whether RAB7B variants contribute to inflammatory disorders, immune deficiencies, or other conditions warrants investigation.

5. Splice isoforms: RAB7B splice isoforms (Rab7b2 and Rab7bx8) have been identified but not functionally characterized. Understanding whether these variants have distinct activities could reveal additional complexity in RAB7B biology.

6. Therapeutic potential: Given RAB7B's role as a negative regulator of TLR signaling, modulation of its activity could potentially be therapeutic in inflammatory conditions. Conversely, in contexts where RAB7B knockdown promotes beneficial outcomes (such as oligodendrocyte differentiation in hypomyelinating disorders), inhibitors might have therapeutic value.

References

• [yang-2004-rab7b-identification-abstract] Yang M, Chen T, Han C, Li N, Wan T, Cao X. Rab7b, a novel lysosome-associated small GTPase, is involved in monocytic differentiation of human acute promyelocytic leukemia cells. Biochem Biophys Res Commun. 2004;318(3):792-9. PMID: 15144907. DOI: 10.1016/j.bbrc.2004.04.115

• [wang-2007-tlr4-degradation-abstract] Wang Y, Chen T, Han C, He D, Liu H, An H, Cai Z, Cao X. Lysosome-associated small Rab GTPase Rab7b negatively regulates TLR4 signaling in macrophages by promoting lysosomal degradation of TLR4. Blood. 2007;110(3):962-71. PMID: 17395780. DOI: 10.1182/blood-2007-01-066027

• [yao-2009-tlr9-abstract] Yao M, Liu X, Li D, Chen T, Cai Z, Cao X. Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages. J Immunol. 2009;183(3):1751-8. PMID: 19587007. DOI: 10.4049/jimmunol.0900249

• [progida-2010-endosome-tgn-abstract] Progida C, Cogli L, Piro F, De Luca A, Bakke O, Bucci C. Rab7b controls trafficking from endosomes to the TGN. J Cell Sci. 2010;123(Pt 9):1480-91. PMID: 20375062. DOI: 10.1242/jcs.051474

• [bucci-2010-receptors-trafficking-fulltext] Bucci C, Bakke O, Progida C. Rab7b and receptors trafficking. Commun Integr Biol. 2010;3(5):401-4. PMID: 21057625. PMCID: PMC2974065. DOI: 10.4161/cib.3.5.12341

• [he-2011-megakaryocyte-abstract] He D, Chen T, Yang M, Zhu X, Wang C, Cao X, Cai Z. Small Rab GTPase Rab7b promotes megakaryocytic differentiation by enhancing IL-6 production and STAT3-GATA-1 association. J Mol Med (Berl). 2011;89(2):137-50. PMID: 20953574. DOI: 10.1007/s00109-010-0689-z

• [horiuchi-2012-rab7-interaction-selectivity-abstract] The Interaction Properties of the Human Rab GTPase Family – A Comparative Analysis Reveals Determinants of Molecular Binding Selectivity. PLoS ONE. 2012. PMID: 22523562. PMCID: PMC3327705. DOI: 10.1371/journal.pone.0034870

• [progida-2012-sorting-receptors-abstract] Progida C, Nielsen MS, Koster G, Bucci C, Bakke O. Dynamics of Rab7b-dependent transport of sorting receptors. Traffic. 2012;13(9):1273-85. PMID: 22708738. DOI: 10.1111/j.1600-0854.2012.01388.x

• [borgdistefano-2015-trafficking-migration-fulltext] Borg Distefano M, Kjos I, Bakke O, Progida C. Rab7b at the intersection of intracellular trafficking and cell migration. Commun Integr Biol. 2015;8(6):e1023492. PMID: 27066171. PMCID: PMC4802807. DOI: 10.1080/19420889.2015.1023492

• [kjos-2017-autophagy-atg4b-abstract] Kjos I, Borg Distefano M, Sætre F, et al. Rab7b modulates autophagic flux by interacting with Atg4B. EMBO Rep. 2017;18(10):1727-1739. PMID: 28835545. PMCID: PMC5623852. DOI: 10.15252/embr.201744069

• [vestre-2021-dc-migration-abstract] Vestre K, Persiconi I, Borg Distefano M, et al. Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton. J Cell Sci. 2021;134(18):jcs259221. PMID: 34494097. PMCID: PMC8487646. DOI: 10.1242/jcs.259221

• [fukushima-2023-oligodendrocyte-abstract] Fukushima N, Shirai R, Sato T, et al. Knockdown of Rab7B, But Not of Rab7A, Which Antagonistically Regulates Oligodendroglial Cell Morphological Differentiation, Recovers Tunicamycin-Induced Defective Differentiation in FBD-102b Cells. J Mol Neurosci. 2023;73:363-374. DOI: 10.1007/s12031-023-02117-y

• [qi-2019-stroke-neuroprotection-abstract] Qi J, Rong Y, Wang L, Xu J, Zhao K. Rab7b Overexpression-Ameliorated Ischemic Brain Damage Following tMCAO Involves Suppression of TLR4 and NF-κB p65. J Mol Neurosci. 2019;68(2):163-170. PMID: 30911939. DOI: 10.1007/s12031-019-01295-y

• [UniProt-Q96AH8] UniProt Consortium. RAB7B - Ras-related protein Rab-7b - Homo sapiens (Human). UniProt Knowledgebase. Accession: Q96AH8. URL: https://www.uniprot.org/uniprotkb/Q96AH8

Citations

1. borgdistefano-2015-trafficking-migration-fulltext.md
2. bucci-2010-receptors-trafficking-fulltext.md
3. fukushima-2023-oligodendrocyte-abstract.md
4. he-2011-megakaryocyte-abstract.md
5. horiuchi-2012-rab7-interaction-selectivity-abstract.md
6. kjos-2017-autophagy-atg4b-abstract.md
7. progida-2010-endosome-tgn-abstract.md
8. progida-2012-sorting-receptors-abstract.md
9. qi-2019-stroke-neuroprotection-abstract.md
10. vestre-2021-dc-migration-abstract.md
11. wang-2007-tlr4-degradation-abstract.md
12. yang-2004-rab7b-identification-abstract.md
13. yao-2009-tlr9-abstract.md

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan
- Verify identity and core definitions for human RAB7B (UniProt Q96AH8), a small GTPase of the Rab family, and set scope distinguishing it from RAB7A.
- Gather recent (especially 2023–2024) and foundational primary literature on molecular function, subcellular localization, effectors/regulators, and pathway roles.
- Extract precise experimental evidence: trafficking routes, innate immune receptor trafficking, actomyosin links and migration phenotypes, key regulators (GAPs/GEFs), and quantitative metrics (colocalization, kinetics, phenotypes).
- Synthesize recent developments and translational links (disease associations, applications).
- Compile a comprehensive, well-cited report with URLs and publication dates.

Identity verification and key concepts
- Target: human RAB7B, UniProt Q96AH8; Ras-related protein Rab-7b. This protein is a small GTPase of the Rab family that cycles between GDP/GTP-bound states to regulate membrane trafficking. Multiple human cell systems explicitly study “human Rab7b,” including HeLa, MelJuSo, and monocyte-derived dendritic cells (MDDCs), confirming the human identity and Rab superfamily membership (Journal of Cell Science, Nov 2014, https://doi.org/10.1242/jcs.155861; Journal of Cell Science, Sep 2018, https://doi.org/10.1242/jcs.216630) (borg2014anovelinteraction pages 1-2, distefano2018tbc1d5controlsthe pages 1-2).
- Family/domains alignment: Functional studies explicitly describe Rab7b as a small GTPase, consistent with P-loop NTPase/Ras superfamily architecture (J Cell Sci 2014; J Cell Sci 2018) (borg2014anovelinteraction pages 1-2, distefano2018tbc1d5controlsthe pages 1-2).

1) Key concepts and definitions with the current understanding
- Molecular role: Rab7b is a small GTPase that regulates late endosomal traffic and retrograde transport to the trans-Golgi network (TGN). Foundational mechanistic work demonstrates that Rab7b localizes to late endosomes/lysosomes and the Golgi/TGN and controls transport between late endosomes and the TGN (J Cell Sci, 2014, https://doi.org/10.1242/jcs.155861; J Cell Sci, 2018, https://doi.org/10.1242/jcs.216630) (borg2014anovelinteraction pages 1-2, distefano2018tbc1d5controlsthe pages 1-2).
- Distinction from Rab7a (conceptual): Rab7a is a master regulator of late endosome–lysosome fusion and autophagy/lysosome function with a broad effector network (e.g., RILP, ORP1L, FYCO1, HOPS, Mon1/Ccz1, retromer), whereas Rab7b has a distinct subcellular routing emphasis toward endosome→TGN transport and has unique interactions (e.g., myosin II, TBC1D5 as a Rab7b GAP) (Biomedical Reviews, Dec 2014, https://doi.org/10.14748/bmr.v25.1049; J Cell Sci, 2018, https://doi.org/10.1242/jcs.216630) (basuray2014rab7athemaster pages 4-7, distefano2018tbc1d5controlsthe pages 1-2, distefano2018tbc1d5controlsthe pages 3-6).

2) Molecular function, regulators/effectors, and quantitative data
- Confirmed molecular functions:
- Endosome↔TGN trafficking: Rab7b controls transport between late endosomes and the TGN; Rab7b-positive structures are Lamp-1+ late endosomes and Golgi/TGN compartments (J Cell Sci, 2014, 2018; URLs above) (borg2014anovelinteraction pages 1-2, distefano2018tbc1d5controlsthe pages 1-2, distefano2018tbc1d5controlsthe pages 3-6).
- Direct actomyosin linkage: A yeast two-hybrid screen identified myosin II as a Rab7b interactor; endogenous Rab7b co-immunoprecipitates with myosin II in human MDDCs; purified recombinant proteins show direct binding (J Cell Sci, 2014) (borg2014anovelinteraction pages 1-2).
- Key effectors/regulators:
- TBC1D5 is a GAP for Rab7b: siRNA screening, in vitro GTPase assays (purified TBC1D5), and retromer (VPS35/VPS29)–augmented GAP activity demonstrate that TBC1D5 catalyzes Rab7b GTP hydrolysis and modulates Rab7b cycling on Golgi/late endosomal membranes (J Cell Sci, Sep 2018, https://doi.org/10.1242/jcs.216630) (distefano2018tbc1d5controlsthe pages 1-2, distefano2018tbc1d5controlsthe pages 3-6).
- Myosin II (actomyosin) functions as a motor/partner: Myosin II depletion or pharmacologic inhibition causes perinuclear clustering/enlargement of Rab7b+ late endosomes and strongly reduces their motility (J Cell Sci, Nov 2014) (borg2014anovelinteraction pages 4-7).
- Quantitative metrics (selected):
- Colocalization: ~69% of Rab7b vesicles colocalize with myosin II (n>100 vesicles analyzed) (J Cell Sci, 2014) (borg2014anovelinteraction pages 4-7).
- Vesicle motility velocities: untreated ~0.34 μm/s; reduced to ~0.19 μm/s with myosin II inhibitor mix (ML7+Y27632); ~0.08 μm/s with blebbistatin; effects reversible upon washout and specific to Rab7b (J Cell Sci, 2014) (borg2014anovelinteraction pages 4-7).
- FRAP kinetics: membrane-binding recovery half-time (t1/2) for Rab7b alone 19.01 ± 0.57 s vs 26.25 ± 0.87 s when co-expressing TBC1D10A (which is not a Rab7b GAP), consistent with distinct cycling regulation (J Cell Sci, 2018) (distefano2018tbc1d5controlsthe pages 3-6).

3) Subcellular localization and trafficking routes controlled
- Localization: Rab7b resides at late endosomes/lysosomes and the Golgi/TGN in human cells (HeLa, MelJuSo, human MDDCs) (J Cell Sci, 2014; J Cell Sci, 2018) (borg2014anovelinteraction pages 1-2, distefano2018tbc1d5controlsthe pages 1-2).
- Trafficking routes: Rab7b governs transport from late endosomes to the TGN (retrograde route), functionally distinct from Rab7a’s strong role in late endosome→lysosome maturation and autophagy/lysosome function (J Cell Sci, 2014; J Cell Sci, 2018; Biomedical Reviews, 2014) (borg2014anovelinteraction pages 1-2, distefano2018tbc1d5controlsthe pages 1-2, basuray2014rab7athemaster pages 4-7).

4) Roles in innate immunity receptor trafficking and signaling
- Multiple studies implicate Rab7b in limiting TLR signaling by promoting receptor trafficking toward degradation and/or retrograde routes. While early sentinel work on TLR4/TLR9 negative regulation by Rab7b is older, a 2014–2018 mechanistic framework places Rab7b at late endosomes and the TGN, with the machinery (actomyosin, TBC1D5/retromer) to influence receptor recycling versus degradation decisions. In the human platelet and immune-cell context, Rab7b’s regulation of late endosome/TGN sorting and actomyosin-dependent vesicle transport provides a mechanistic basis for negative regulation of activated receptor pools, although the most precise human TLR4 degradation data predate 2020 (see also sections above on localization, motors, and GAP regulation) (borg2014anovelinteraction pages 1-2, borg2014anovelinteraction pages 4-7, distefano2018tbc1d5controlsthe pages 1-2).

5) Interactions with the actomyosin system and impacts on cell migration
- Direct physical interaction with myosin II: Rab7b binds myosin II (validated by Y2H, co-IP of endogenous proteins in human MDDCs, and recombinant pull-downs), indicating myosin II acts as an effector/motor for Rab7b-positive endosomes (J Cell Sci, 2014) (borg2014anovelinteraction pages 1-2).
- Cell migration and cytoskeletal phenotypes: Rab7b depletion reduces stress-fiber formation, cell adhesion on fibronectin, and delays migration; mechanistically, Rab7b depletion lowers GTP-RhoA and decreases phosphorylated myosin light chain (MLC), linking Rab7b to contractility regulation (J Cell Sci, 2014) (borg2014anovelinteraction pages 1-2).
- Quantitative transport phenotypes: Myosin II inhibition markedly reduces Rab7b vesicle velocities and causes perinuclear clustering/enlargement of Lamp-1+ late endosomes, without comparable effects on Rab5, Rab7a, or Rab9 compartments, underscoring specificity (J Cell Sci, 2014) (borg2014anovelinteraction pages 4-7).

6) Distinctions from RAB7A (clear mechanistic contrasts)
- Localization and route preference: Rab7a—late endosome→lysosome fusion/maturation and broad lysosome function; Rab7b—late endosome↔TGN retrograde traffic, with strong Golgi/TGN association (Biomedical Reviews, 2014; J Cell Sci, 2014; J Cell Sci, 2018) (basuray2014rab7athemaster pages 4-7, borg2014anovelinteraction pages 1-2, distefano2018tbc1d5controlsthe pages 1-2).
- Effector/regulator sets: Rab7a’s canonical effectors include RILP, ORP1L, FYCO1, HOPS, Mon1/Ccz1 and others; Rab7b is regulated by TBC1D5 as a GAP and engages myosin II as a direct binding partner/effector (Biomedical Reviews, 2014; J Cell Sci, 2018; J Cell Sci, 2014) (basuray2014rab7athemaster pages 4-7, distefano2018tbc1d5controlsthe pages 1-2, borg2014anovelinteraction pages 1-2).
- Functional outcomes: Rab7a broadly controls lysosomal degradation, autophagy-lysosome fusion and receptor downregulation; Rab7b fine-tunes late endosome→TGN routing and couples endosomal transport to actomyosin and migration programs (Biomedical Reviews, 2014; J Cell Sci, 2014; J Cell Sci, 2018) (basuray2014rab7athemaster pages 4-7, borg2014anovelinteraction pages 1-2, distefano2018tbc1d5controlsthe pages 1-2).

7) Recent developments and latest research (2023–2024 priority), applications and disease links
- Adipocyte autophagy/lipid metabolism axis (2024): A study in Autophagy (Apr 2024) shows that TIGAR overexpression elevates LRRK2 and drives its interaction with RAB7B in adipocytes, suppressing lysosomal degradation of lipid droplets and impairing macroautophagy and chaperone-mediated autophagy. Mechanistically, active RAB7B in lipid-droplet fractions declines ~2–3× upon TIGAR overexpression (RILP-affinity assay). Pharmacologic inhibition of LRRK2 (ML282) or adipose-targeted delivery of a LRRK2 inhibitor (DNL201 nanoemulsion) reverses lipid accumulation and restores autophagy markers in mice, indicating a functional LRRK2–RAB7B axis and nominating RAB7B as a node in metabolic disease biology and a potential therapeutic target (Autophagy, Apr 2024, https://doi.org/10.1080/15548627.2024.2338576) (zhang2024tigarexacerbatesobesity pages 12-15).
- Regulation by GAPs (2018 foundation for current work): TBC1D5 is a Rab7b GAP whose activity is augmented by retromer, providing a mechanistic handle for modulating Rab7b cycling in cells—relevant for ongoing efforts that exploit retromer- and GAP-dependent endosomal routing in disease models (J Cell Sci, 2018, https://doi.org/10.1242/jcs.216630) (distefano2018tbc1d5controlsthe pages 1-2, distefano2018tbc1d5controlsthe pages 3-6).

8) Current applications and real-world implementations
- Targeting the LRRK2–RAB7B axis in adipose tissue: The 2024 Autophagy report deployed an adipose-tropic nanoemulsion (DNL201-NE) to deliver an LRRK2 inhibitor in a TIGAR-overexpressing mouse model, correcting autophagy defects and lipid accumulation. This provides an in vivo implementation of pathway modulation that functionally engages RAB7B activity/state (Autophagy, Apr 2024, https://doi.org/10.1080/15548627.2024.2338576) (zhang2024tigarexacerbatesobesity pages 12-15).

9) Expert opinions and analysis
- Mechanistic synthesis: The combined evidence places RAB7B as a late endosome/TGN trafficking regulator that directly couples to the actomyosin system to coordinate vesicle transport and cell migration programs. Its cycling is constrained by TBC1D5 (with retromer enhancement), and its activity can be functionally modulated by upstream signaling hubs such as LRRK2 in disease-relevant tissues (borg2014anovelinteraction pages 1-2, borg2014anovelinteraction pages 4-7, distefano2018tbc1d5controlsthe pages 1-2, distefano2018tbc1d5controlsthe pages 3-6, zhang2024tigarexacerbatesobesity pages 12-15).
- Distinction from Rab7a is not merely paralogous redundancy but reflects divergent effector networks and routing priorities (Rab7a for lysosome maturation/autophagy; Rab7b for endosome→TGN retrograde movement and actomyosin coupling). This division likely underlies differing phenotypic consequences upon perturbation in immune cells, cancer models, and metabolic tissues (basuray2014rab7athemaster pages 4-7, borg2014anovelinteraction pages 1-2, distefano2018tbc1d5controlsthe pages 1-2).

10) Relevant statistics and data from recent studies
- Colocalization and motility: 69% Rab7b–myosin II colocalization; velocities 0.34 vs 0.19 vs 0.08 μm/s under graded myosin II inhibition; perinuclear clustering/enlargement of Rab7b+ Lamp-1+ late endosomes upon myosin II loss (J Cell Sci, 2014, https://doi.org/10.1242/jcs.155861) (borg2014anovelinteraction pages 4-7).
- FRAP kinetics: Rab7b t1/2 membrane recovery 19.01 ± 0.57 s (baseline) versus 26.25 ± 0.87 s with TBC1D10A coexpression (not a Rab7b GAP), reflecting altered cycling kinetics under different regulatory contexts (J Cell Sci, 2018, https://doi.org/10.1242/jcs.216630) (distefano2018tbc1d5controlsthe pages 3-6).
- Adipocyte disease model: TIGAR overexpression reduces active RAB7B on lipid droplets by ~2–3× and this correlates with suppressed lipid droplet lysosomal degradation; pharmacologic LRRK2 inhibition restores autophagy markers and reduces lipid accumulation in vivo (Autophagy, 2024, https://doi.org/10.1080/15548627.2024.2338576) (zhang2024tigarexacerbatesobesity pages 12-15).

Conclusions
Human RAB7B (UniProt Q96AH8) is a small Rab-family GTPase localized to late endosomes/lysosomes and the Golgi/TGN, where it regulates retrograde transport from late endosomes to the TGN and directly couples endosomal motility to the actomyosin cytoskeleton via myosin II. Its GTPase cycle is controlled by the GAP TBC1D5, whose activity is strengthened by retromer. Quantitatively, Rab7b colocalizes with myosin II on ~69% of vesicles and exhibits pronounced reductions in vesicle velocities upon myosin II inhibition; its membrane-binding dynamics are measurable by FRAP and sensitive to co-regulators. Recent work (2024) links RAB7B activity to autophagy and lipid metabolism through a TIGAR–LRRK2–RAB7B axis in adipocytes, with in vivo pharmacologic intervention demonstrating reversibility of pathological phenotypes. Together, these data delineate a specialized role for RAB7B—distinct from RAB7A—in endosome→TGN routing and cytoskeletal coordination with direct implications for immune signaling regulation, cell migration, and metabolic disease pathways (borg2014anovelinteraction pages 1-2, borg2014anovelinteraction pages 4-7, distefano2018tbc1d5controlsthe pages 1-2, distefano2018tbc1d5controlsthe pages 3-6, basuray2014rab7athemaster pages 4-7, zhang2024tigarexacerbatesobesity pages 12-15).

References

1. (borg2014anovelinteraction pages 1-2): Marita Borg, Oddmund Bakke, and Cinzia Progida. A novel interaction between rab7b and actomyosin reveals a dual role in intracellular transport and cell migration. Journal of Cell Science, 127:4927-4939, Nov 2014. URL: https://doi.org/10.1242/jcs.155861, doi:10.1242/jcs.155861. This article has 46 citations and is from a domain leading peer-reviewed journal.

2. (distefano2018tbc1d5controlsthe pages 1-2): Marita Borg Distefano, Linda Hofstad Haugen, Yan Wang, Harmonie Perdreau-Dahl, Ingrid Kjos, Da Jia, Jens Preben Morth, Jacques Neefjes, Oddmund Bakke, and Cinzia Progida. Tbc1d5 controls the gtpase cycle of rab7b. Journal of Cell Science, Sep 2018. URL: https://doi.org/10.1242/jcs.216630, doi:10.1242/jcs.216630. This article has 45 citations and is from a domain leading peer-reviewed journal.

3. (basuray2014rab7athemaster pages 4-7): Soumik BasuRay. Rab7a: the master regulator of vesicular trafficking. Biomedical Reviews, 25:67-81, Dec 2014. URL: https://doi.org/10.14748/bmr.v25.1049, doi:10.14748/bmr.v25.1049. This article has 2 citations.

4. (distefano2018tbc1d5controlsthe pages 3-6): Marita Borg Distefano, Linda Hofstad Haugen, Yan Wang, Harmonie Perdreau-Dahl, Ingrid Kjos, Da Jia, Jens Preben Morth, Jacques Neefjes, Oddmund Bakke, and Cinzia Progida. Tbc1d5 controls the gtpase cycle of rab7b. Journal of Cell Science, Sep 2018. URL: https://doi.org/10.1242/jcs.216630, doi:10.1242/jcs.216630. This article has 45 citations and is from a domain leading peer-reviewed journal.

5. (borg2014anovelinteraction pages 4-7): Marita Borg, Oddmund Bakke, and Cinzia Progida. A novel interaction between rab7b and actomyosin reveals a dual role in intracellular transport and cell migration. Journal of Cell Science, 127:4927-4939, Nov 2014. URL: https://doi.org/10.1242/jcs.155861, doi:10.1242/jcs.155861. This article has 46 citations and is from a domain leading peer-reviewed journal.

6. (zhang2024tigarexacerbatesobesity pages 12-15): Tianjie Zhang, Ke-gang Linghu, Jia Tan, Mingming Wang, Diao Chen, Yan Shen, Junchao Wu, Ming-jun Shi, Yuxia Zhou, Lei Tang, Lirong Liu, Zheng-Hong Qin, and Bing Guo. Tigar exacerbates obesity by triggering lrrk2-mediated defects in macroautophagy and chaperone-mediated autophagy in adipocytes. Autophagy, 20:1741-1761, Apr 2024. URL: https://doi.org/10.1080/15548627.2024.2338576, doi:10.1080/15548627.2024.2338576. This article has 18 citations and is from a domain leading peer-reviewed journal.

Citations

1. borg2014anovelinteraction pages 1-2
2. borg2014anovelinteraction pages 4-7
3. zhang2024tigarexacerbatesobesity pages 12-15
4. https://doi.org/10.1242/jcs.155861;
5. https://doi.org/10.1242/jcs.216630
6. https://doi.org/10.14748/bmr.v25.1049;
7. https://doi.org/10.1080/15548627.2024.2338576
8. https://doi.org/10.1242/jcs.155861
9. https://doi.org/10.1242/jcs.155861,
10. https://doi.org/10.1242/jcs.216630,
11. https://doi.org/10.14748/bmr.v25.1049,
12. https://doi.org/10.1080/15548627.2024.2338576,

RAB7B: A Small GTPase in Endosomal Trafficking and Immune Regulation

Gene and Protein Overview

RAB7B (Ras-related protein Rab-7b) is a human gene encoding a small GTPase of the Rab family, part of the Ras superfamily of regulatory proteins. It was first identified in 2004 by Cao and colleagues in studies of acute promyelocytic leukemia cell differentiation (pmc.ncbi.nlm.nih.gov). RAB7B shares about 60–70% amino acid identity with the better-known RAB7A protein (pmc.ncbi.nlm.nih.gov) (www.mdpi.com). Like other Rab GTPases, Rab7b contains conserved P-loop NTP-binding motifs and switches between an active GTP-bound state and an inactive GDP-bound state to regulate vesicle trafficking (pmc.ncbi.nlm.nih.gov). This protein is geranylgeranylated at the C-terminus, anchoring it to cellular membranes when active. Importantly, Rab7b is not merely a redundant isoform of Rab7a – emerging research demonstrates that Rab7b has distinct localization, effectors, and functions in the cell (pmc.ncbi.nlm.nih.gov) (www.mdpi.com). (Notably, Rab7b has been referred to as Rab42 in some contexts, particularly in rodent studies (pmc.ncbi.nlm.nih.gov), but RAB7B is the official human gene symbol corresponding to UniProt Q96AH8.)

Localization and Molecular Characteristics

Rab7b is primarily an intracellular protein associated with late endosomes, lysosomes, and the trans-Golgi network (TGN). In resting cells, wild-type Rab7b localizes to late endosomal/lysosomal compartments, whereas the GTP-bound (active) form can accumulate at the Golgi/TGN (pubmed.ncbi.nlm.nih.gov). In fact, Rab7b is observed on membranes of late endosomes and lysosomes, as well as the TGN/Golgi, consistent with its role in directing traffic between these compartments (pmc.ncbi.nlm.nih.gov). This localization pattern contrasts with Rab7a, which is found largely on late endosomes and lysosomes moving toward degradation pathways (pmc.ncbi.nlm.nih.gov). Rab7b’s cycling between lysosomes and Golgi is functionally significant: active Rab7b helps mediate retrograde transport from endosomal compartments back to the TGN, while the GDP-bound form resides on lysosomal membranes (pubmed.ncbi.nlm.nih.gov).

Structurally, Rab7b conforms to the typical small GTPase (Ras) fold, including five conserved G-motifs for nucleotide binding and hydrolysis. Biochemically, it binds guanine nucleotide and possesses intrinsic GTPase activity that is regulated by GEFs (guanine exchange factors) and GAPs (GTPase activating proteins) like other Rabs (pmc.ncbi.nlm.nih.gov). A key distinction of Rab7b is its effector interactions: for example, Rab7b does not bind RILP (Rab-interacting lysosomal protein), an effector that Rab7a uses to recruit dynein motors (pmc.ncbi.nlm.nih.gov). This was shown experimentally (Bucci et al., 2010) and underscores “profound differences between Rab7 and Rab7b” in their molecular machinery (pmc.ncbi.nlm.nih.gov). Instead, Rab7b has unique partners (discussed below) that link it to actin-based motors and signaling molecules, highlighting a specialized role distinct from Rab7a (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Role in Vesicular Trafficking (Endosome–TGN Transport)

One of Rab7b’s primary functions is regulating membrane trafficking between late endosomes and the TGN. Progida et al. (2010) demonstrated that Rab7b is required for proper transport of certain cargo from endosomes back to the Golgi (pubmed.ncbi.nlm.nih.gov). In Rab7b-depleted cells or dominant-negative Rab7b mutants, sorting receptors like cation-independent mannose-6-phosphate receptor (CI-MPR) and TGN46 become mislocalized, indicating defective retrograde trafficking (pubmed.ncbi.nlm.nih.gov). This causes downstream effects such as impaired maturation of lysosomal enzyme cathepsin D and increased secretion of lysosomal hydrolases that should normally be recycled to lysosomes (pubmed.ncbi.nlm.nih.gov). Indeed, loss of Rab7b function led to accumulation of late endosomal markers (e.g., CI-MPR, cathepsin D) and mis-sorting of lysosomal enzymes, while general secretory transport (tested by VSV-G protein trafficking to the plasma membrane) remained unaffected (pubmed.ncbi.nlm.nih.gov). Furthermore, blocking Rab7b prevented retrograde delivery of internalized toxins: cells lacking Rab7b cannot efficiently transport cholera toxin B or Shiga toxin to the Golgi apparatus (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These findings indicate Rab7b is a key regulator of the retrograde pathway from late endosomes to the TGN, which is crucial for recycling sorting receptors and certain toxins’ routes.

By contrast, Rab7a controls an anterograde endolysosomal pathway – directing cargos toward late endosomes and lysosomes for degradation (pmc.ncbi.nlm.nih.gov). Rab7b’s specialization in the retrograde route means it essentially acts in opposition to Rab7a: Rab7a facilitates cargo degradation in lysosomes, whereas Rab7b retrieves selected membrane proteins (like CI-MPR) from late endosomes back to Golgi for reuse (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This division of labor is reflected in their phenotypes: for example, epidermal growth factor receptor (EGFR) down-regulation requires Rab7a but not Rab7b (pubmed.ncbi.nlm.nih.gov), whereas CI-MPR recycling and Shiga toxin retrograde transport specifically depend on Rab7b (pmc.ncbi.nlm.nih.gov). Thus, Rab7b is fundamental for maintaining proper receptor trafficking balance between degradation and recycling routes (pmc.ncbi.nlm.nih.gov).

Mechanistically, Rab7b likely engages distinct tethering factors and motors to mediate this retrograde transport. Its inability to recruit RILP implies Rab7b uses different effectors than Rab7a for movement along cytoskeletal tracks (pmc.ncbi.nlm.nih.gov). Supporting this, Rab7b was found to interact with the actin motor myosin II (discussed below) rather than exclusively microtubule motors (pmc.ncbi.nlm.nih.gov). The net effect is that Rab7b-positive vesicles are directed toward the perinuclear Golgi region, ensuring sorting receptors (like mannose-6-phosphate receptors) cycle properly. In summary, Rab7b’s key role in vesicular traffic is controlling the late endosome–TGN route, thereby influencing the distribution of lysosomal enzymes and certain receptors (pmc.ncbi.nlm.nih.gov). This activity positions Rab7b as an important regulator of lysosome function and homeostasis indirectly, by governing what gets sent back to Golgi versus sent for degradation.

Regulation of Immune Receptor Signaling

Rab7b has attracted particular interest for its role in the immune system, especially in the trafficking and signaling of Toll-like receptors (TLRs). Studies from Cao’s group (2007–2009) identified Rab7b as a negative regulator of inflammatory signaling: Rab7b promotes lysosomal degradation of TLR4 and TLR9, thereby dampening their signaling (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In macrophages, overexpression of Rab7b or its activation leads to enhanced delivery of TLR4 to lysosomes, resulting in reduced TLR4 protein on the cell surface and blunted TLR4-dependent NF-κB signaling (pmc.ncbi.nlm.nih.gov). Wang et al. (2007) showed that Rab7b overexpression in human macrophages decreased cytokine production (such as TNF-α and IL-6) after TLR4 (LPS) stimulation, by accelerating TLR4 turnover in lysosomes (pmc.ncbi.nlm.nih.gov). Conversely, inhibiting Rab7b caused prolonged TLR4 signaling. This establishes Rab7b as part of a feedback loop limiting Toll-like receptor signaling intensity.

Similarly, Rab7b suppresses TLR9-mediated signaling in plasmacytoid dendritic cells and macrophages. Yao et al. (2009) reported that Rab7b co-localizes with activated TLR9 in LAMP1-positive late endosomes/lysosomes and facilitates TLR9 degradation (pubmed.ncbi.nlm.nih.gov). Notably, they found that engaging TLR9 (with CpG DNA) transiently causes a decrease in Rab7b expression, via ERK/p38 MAPK signaling, suggesting cells temporarily relieve Rab7b’s brake to allow an initial immune response (pubmed.ncbi.nlm.nih.gov). Then Rab7b comes into play to terminate signaling: Rab7b down-regulates TLR9-triggered production of pro-inflammatory cytokines (TNFα, IL-6) and Type I interferons by targeting TLR9 for destruction (pubmed.ncbi.nlm.nih.gov). Macrophages lacking Rab7b showed elevated and sustained activation of MAPK and NF-κB pathways upon TLR9 stimulation (pubmed.ncbi.nlm.nih.gov). In sum, Rab7b acts as a negative regulator of innate immune receptors, preventing overactivation by routing receptors to the lysosomal pathway for degradation. This mechanism has important implications: overactive TLR signaling is linked to autoimmune inflammation (e.g., inappropriate TLR9 activation contributes to systemic lupus erythematosus) (pubmed.ncbi.nlm.nih.gov). By promoting TLR degradation, Rab7b helps maintain immune homeostasis, and defects in Rab7b-mediated trafficking could exacerbate inflammatory or autoimmune conditions (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Conversely, enhancing Rab7b function might be protective in such settings. Indeed, Rab7b expression is dynamically regulated during immune activation – for example, dendritic cells (DCs) down-regulate RAB7B upon LPS-induced maturation (when they need high TLR signaling), whereas monocytes up-regulate RAB7B in response to LPS or during phorbol ester-driven differentiation to macrophages (pmc.ncbi.nlm.nih.gov). This reciprocal pattern aligns with Rab7b’s role: immature macrophages increase Rab7b to prevent excessive inflammation, while maturing DCs temporarily suppress Rab7b to maximize antigen-triggered signaling (pmc.ncbi.nlm.nih.gov). Overall, Rab7b serves as an intracellular “brake” on TLR pathways, ensuring that pro-inflammatory signals can be shut off appropriately by trafficking receptors into the degradation route (pubmed.ncbi.nlm.nih.gov).

Beyond TLRs, Rab7b may influence other immune receptors and processes. A study in platelets found that Rab7b (in concert with a calpain–myosin9 pathway) regulates TLR4 storage in platelet alpha-granules, affecting how platelets respond to LPS (pmc.ncbi.nlm.nih.gov). This suggests Rab7b’s role in trafficking extends to secretory granules in various cell types. Moreover, by controlling endosomal dynamics, Rab7b could modulate antigen presentation or phagocytic pathway maturation in macrophages and DCs (although Rab7a has a more pronounced role in phagolysosome maturation) (pmc.ncbi.nlm.nih.gov). Importantly, expert reviews (Bucci et al., 2010) have highlighted Rab7b as a key factor “opening a revised scenario” for TLR signaling regulation – rather than being solely biochemically regulated, TLR signaling is also controlled by Rab7b-mediated receptor trafficking (pmc.ncbi.nlm.nih.gov). This crosstalk between vesicle transport and signaling is a paradigm increasingly appreciated in cell biology, and Rab7b is a prime example of a trafficking regulator with direct impact on immune cell function.

Interaction with Cytoskeleton and Cell Migration

While Rab7b was initially characterized for its trafficking roles, recent research uncovered a surprising link between Rab7b and the actin cytoskeleton, with implications for cell migration. Borg et al. (2014) first reported a direct interaction between Rab7b and non-muscle myosin II (the motor protein that drives actomyosin contractility) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Using yeast two-hybrid screening and co-immunoprecipitation, they found Rab7b binds myosin II heavy chain, making myosin II a bona fide effector of Rab7b (pmc.ncbi.nlm.nih.gov). Functionally, disrupting myosin II (pharmacologically or by siRNA) caused Rab7b-bearing vesicles to alter their dynamics, suggesting Rab7b’s transport function is dependent on actomyosin activity (pmc.ncbi.nlm.nih.gov). This was one of the first indications that a Rab GTPase (traditionally linked to microtubule-based movement) can directly coordinate with the actin motor system.

Further investigations revealed that Rab7b not only rides on actin tracks but also actively influences actin organization. Rab7b-depleted cells showed reductions in stress fibers and altered cell morphology (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Mechanistically, Rab7b was found to affect the signaling that controls myosin II. Specifically, Rab7b depletion led to a strong decrease in active RhoA levels and a corresponding drop in myosin II light chain (MLC) phosphorylation (pmc.ncbi.nlm.nih.gov). RhoA is a small GTPase that via ROCK kinase induces MLC phosphorylation to activate myosin II contractility. Thus, Rab7b somehow promotes RhoA–ROCK signaling. The 2014 study proposed that by coupling vesicle trafficking to RhoA activation, Rab7b coordinates actin remodeling with membrane transport, thereby impacting processes like cell adhesion and motility (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In line with this, cells lacking Rab7b had defects in forming polarized actomyosin structures and migrated more poorly in wound-healing assays (suggesting Rab7b contributes to efficient cell movement).

A more recent 2021 study (Vestre et al., 2021) in Journal of Cell Science illuminated Rab7b’s role in immune cell migration with even greater detail. Dendritic cells (which migrate from tissues to lymph nodes during immune responses) require controlled rear contraction and lysosome positioning for fast migration. Rab7b was identified as the “missing physical link” connecting lysosomes to the actomyosin cytoskeleton (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). The researchers showed that Rab7b interacts with the lysosomal calcium channel TRPML1 (also known as MCOLN1) on lysosome membranes (pubmed.ncbi.nlm.nih.gov). Through this interaction, Rab7b positions lysosomes at the cell rear and facilitates localized Ca²⁺ release via TRPML1. The Ca²⁺, in turn, activates myosin II motor activity right where the cell needs to contract for forward movement (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). In Rab7b-knockout DCs, lysosomes failed to properly link to the actomyosin network: the cells showed significantly reduced MLC phosphorylation and reduced activation of TFEB (a transcription factor activated by lysosomal signals that is required for optimal migration) (pubmed.ncbi.nlm.nih.gov). Functionally, loss of Rab7b slowed DC migration in both 2D and 3D environments (pubmed.ncbi.nlm.nih.gov). By enabling lysosome-to-cytoskeleton coupling, Rab7b thus ensures that myosin II contracts at the cell’s rear, a crucial step for cell locomotion (particularly in dense 3D matrices where cells move in an amoeboid manner). This finding is a striking example of a trafficking protein influencing cell motility and has broader implications for how internal organelles contribute to cell mechanics.

In summary, Rab7b plays a dual role: (1) as a trafficking regulator and (2) as a coordinator of cytoskeletal dynamics. By binding myosin II and interacting with lysosomal Ca²⁺ channels, Rab7b can control local actin filament remodeling, cell polarity, and movement (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). These discoveries expand the functional repertoire of Rab GTPases, showing that Rab7b links membrane transport to cell migration – particularly important in migratory immune cells like dendritic cells. Experts have noted that this places Rab7b “at the intersection of intracellular trafficking and cell migration” (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), underlining its significance in cell biology beyond simple vesicle shuttling.

Expression Patterns and Regulation

The expression of RAB7B varies across cell types and is regulated during cell differentiation and activation, reflecting its specialized functions. Rab7b is highly expressed in cells of the monocyte–macrophage lineage and related immune cells. For instance, human CD14⁺ monocytes, monocyte-derived immature dendritic cells, and promyelocytic leukemia cell lines show abundant RAB7B expression (pmc.ncbi.nlm.nih.gov). During monocytic differentiation (such as HL-60 promyelocytic cells treated to become macrophage-like), RAB7B levels rise significantly (pmc.ncbi.nlm.nih.gov). This induction aligns with the need for enhanced endolysosomal trafficking capacity as monocytes mature into phagocytes. On the other hand, when dendritic cells mature (e.g., upon LPS stimulation), RAB7B is down-regulated (pmc.ncbi.nlm.nih.gov). This makes sense in context: immature DCs (which are actively sampling antigens but not yet strongly stimulating T cells) keep Rab7b high – possibly to avoid premature inflammatory signaling – whereas mature DCs (which are presenting antigens and secreting cytokines) lower Rab7b to allow maximal TLR signaling during the crucial activation window (pmc.ncbi.nlm.nih.gov). Such differential regulation underscores Rab7b’s role as an immune modulator.

Rab7b expression has also been detected in other specialized contexts. There is evidence of alternative splicing of RAB7B in mice, yielding isoforms (Rab7b2, Rab7bx8) that are expressed in certain tissues (e.g. during osteoclast differentiation) (www.mdpi.com) (www.mdpi.com). While these splice variants have not been well-characterized in human cells, their existence suggests additional layers of regulation and potentially tissue-specific functions for Rab7b. Hormonal and stress signals may also influence Rab7b levels indirectly; for instance, the TLR9 signaling study noted that TLR9 engagement transiently inhibits Rab7b expression via MAPK activation (pubmed.ncbi.nlm.nih.gov), illustrating a feedback mechanism where an immune stimulus modulates the trafficking machinery. No known genetic disorders are directly caused by RAB7B mutations to date (unlike RAB7A, where certain mutations cause Charcot-Marie-Tooth neuropathy type 2B), but changes in Rab7b expression or activity could contribute to pathological states as discussed below.

Pathophysiological Significance and Recent Developments

Given its role in key cellular pathways, Rab7b has been implicated in several pathophysiological contexts. In immunity, as mentioned, Rab7b’s ability to restrain TLR signaling suggests a connection to autoimmune and inflammatory diseases. For example, overactivation of TLR9 is a factor in lupus, and Rab7b helps suppress TLR9-driven production of interferon and cytokines (pubmed.ncbi.nlm.nih.gov). Some studies have proposed that increasing Rab7b activity or mimicking its function might ameliorate autoimmune inflammation by accelerating the removal of TLRs and thus dampening the immune response (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Conversely, a failure to upregulate Rab7b appropriately could prolong inflammation. In line with this, platelet hyperreactivity in conditions like sepsis could be linked to altered Rab7b-mediated TLR4 trafficking (pmc.ncbi.nlm.nih.gov), though more research is needed.

An interesting area is Rab7b’s role in diseases involving intracellular pathogens or toxins. Certain bacteria and toxins hijack endosomal transport; Rab7b’s function in retrograde transport means it can influence how pathogens exploit host pathways. A notable example is Shiga toxin (from pathogenic E. coli), which travels from endosomes to the Golgi/ER to exert its toxic effect. Rab7b facilitates the transport of Shiga toxin to the Golgi (pmc.ncbi.nlm.nih.gov). This implies that inhibiting Rab7b could actually protect cells from Shiga toxin by trapping the toxin in endosomes and routing it to lysosomes for degradation. In fact, researchers have speculated that lack of Rab7b might be beneficial in conditions like hemolytic uremic syndrome (HUS), where Shiga toxin is the causative agent (www.mdpi.com). While not yet demonstrated in animal models, this points to a potential host-defense strategy: transiently blocking Rab7b during certain infections might reduce toxin or pathogen dissemination via the retrograde route.

Rab7b’s emerging role in cell migration also suggests relevance to cancer metastasis and tissue remodeling. Efficient migration of dendritic cells (and possibly other immune cells) requires Rab7b (pubmed.ncbi.nlm.nih.gov), so tumors that want to evade immune detection might downregulate Rab7b to impair DC trafficking to lymph nodes (though this is hypothetical). On the other hand, some cancer cells co-opt lysosome positioning and RhoA signaling for invasion; whether Rab7b contributes to tumor cell motility is not yet clearly shown, but it remains an open question.

Beyond the immune system, Rab7b has been found to function in pigment cell biology. A 2020 study by Marubashi et al. discovered that Rab7b in keratinocytes regulates the turnover of melanosomes (pigment-containing organelles). Keratinocytes acquire melanosomes from melanocytes and eventually degrade them to modulate skin pigmentation. Rab7b (there termed Rab7B/Rab42) was one of the key Rabs recruited to melanosome-containing compartments, and knocking out Rab7b significantly delayed the degradation of melanosomal proteins in keratinocytes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In Rab7b-deficient keratinocytes, internalized melanosomes persisted longer, indicating Rab7b normally promotes their lysosome-dependent breakdown (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This finding reveals a role for Rab7b in the skin’s response to UV exposure and pigmentation processes. It also suggests that variations in Rab7b activity might influence conditions like hyperpigmentation or melanosome storage diseases.

Perhaps the most striking recent development involving Rab7b is its connection to a neurogenetic disease: Pelizaeus-Merzbacher disease (PMD), a rare leukodystrophy caused by misfolding of the proteolipid protein PLP1 in oligodendrocytes. A 2024 study applied CRISPR/CasRx to knock down RAB7B in oligodendroglial cells carrying a mutant PLP1, and found that this unexpectedly improved cell morphology (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The mutant PLP1 normally accumulates in the ER, causing stress, but when Rab7b was reduced, more of the mutant protein trafficked to LAMP1-positive lysosomal compartments for degradation (pmc.ncbi.nlm.nih.gov). In essence, decreasing Rab7b shifted the balance toward the degradative (Rab7a-driven) pathway, helping the cells dispose of misfolded myelin protein and alleviating ER stress (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The knockdown of Rab7b restored more normal cell shape and increased markers of oligodendrocyte differentiation in this model (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These findings suggest that Rab7b inhibition could be a therapeutic strategy in diseases where harmful proteins need enhanced lysosomal clearance. By removing Rab7b’s retrograde retrieval function, more cargo is sent to lysosomes via Rab7a, as evidenced by increased transport of mutant PLP1 to LAMP1⁺ lysosomes when Rab7b was silenced (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Thus, Rab7b joins the growing list of trafficking regulators that may be drug targets in protein-misfolding disorders. The PMD study (Neurosci. Insights, Sept 2024) highlights how manipulating intracellular traffic can ameliorate disease phenotypes – in this case, Rab7b knockdown partially rescued a myelination defect (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). It exemplifies a real-world implementation of Rab7b research, moving from basic cell biology to a potential therapeutic approach.

Expert Commentary and Conclusion

Experts in the field note that Rab7b exemplifies the nuanced specialization within the Rab GTPase family. As reviewed by Bucci et al. (2010), although Rab7b was initially assumed to mirror Rab7a, it in fact “regulates transport from late endosomes to the TGN” and is “fundamental for trafficking of several receptors”, distinct from Rab7a’s role (pmc.ncbi.nlm.nih.gov). This revised understanding, they argue, requires thinking of endosomal trafficking not as a one-way route to destruction, but as a network of intersecting pathways that fine-tune signaling and homeostasis (pmc.ncbi.nlm.nih.gov). Similarly, Progida and colleagues (2015) discussed Rab7b’s ability to control actin-based processes, positing that Rab7b provides a link between organelle positioning and cell migratory behavior (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In their view, Rab7b’s dual roles ensure that immune cells can coordinate their internal remodeling with their external function (e.g., degrading receptors while moving to where they are needed) (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov).

In conclusion, RAB7B is a multifunctional small GTPase that plays crucial roles in endosomal recycling, immune regulation, and cytoskeletal dynamics. Its key functions – promoting retrograde transport to the Golgi and targeting immune receptors to lysosomes – position Rab7b as a modulator of both protein trafficking fidelity and inflammatory signaling. Rab7b operates at the crossroads of pathways: it ensures lysosomal enzymes and receptors are correctly routed, and it physically links lysosome positioning to cell movement. Recent research (2020–2024) has expanded our understanding of Rab7b, uncovering its involvement in processes as diverse as skin pigmentation, dendritic cell motility, and myelin disease pathology. These findings suggest that Rab7b’s activity must be finely balanced: too little Rab7b can enhance degradation pathways (useful for clearing unwanted proteins or toxins), whereas too much Rab7b might suppress immune responsiveness or alter cellular dynamics in undesired ways. Ongoing studies continue to explore Rab7b’s interactome and regulation, with emerging interest in it as a therapeutic target for modulating intracellular traffic in disease. As an authoritative summary in 2021 noted, “Rab7b is distinct from Rab7a” in function and even absence of Rab7b can be beneficial in certain disease contexts (www.mdpi.com). Thus, RAB7B has evolved into an important subject of study in cell and medical biology – a testament to how a single “letter change” in the Rab family (from 7A to 7B) yields a qualitatively new layer of cellular control.

References:

• Yang et al., 2004 – Rab7b identified in monocytic differentiation (pmc.ncbi.nlm.nih.gov) (Biochem. Biophys. Res. Commun., May 2004)
• Wang et al., 2007 – Rab7b promotes TLR4 degradation, limiting cytokine signaling (pmc.ncbi.nlm.nih.gov) (Blood, Aug 2007)
• Yao et al., 2009 – Rab7b down-regulates TLR9 signaling via lysosomal targeting (pubmed.ncbi.nlm.nih.gov) (J. Immunol., Aug 2009)
• Progida et al., 2010 – Rab7b required for endosome-to-TGN transport (CI-MPR, etc.) (pubmed.ncbi.nlm.nih.gov) (J. Cell Sci., May 2010)
• Bucci et al., 2010 – Rab7b and receptor trafficking (expert commentary) (pmc.ncbi.nlm.nih.gov) (Commun. Integr. Biol., Sep 2010)
• Borg et al., 2014 – Rab7b interacts with actomyosin, dual role in transport and migration (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) (J. Cell Sci., 2014)
• Marubashi & Fukuda, 2020 – Rab7b on melanosomes, promotes their degradation (pmc.ncbi.nlm.nih.gov) (Cell Struct. Funct., Feb 2020)
• Vestre et al., 2021 – Rab7b links lysosomes to actin, required for fast DC migration (pubmed.ncbi.nlm.nih.gov) (J. Cell Sci., Sep 2021)
• Fukushima et al., 2024 – Rab7b knockdown alleviates PLP1 mutant stress in oligodendrocytes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) (Neurosci. Insights, Sep 2024)

Citations

1. AnnotationURLCitation(end_index=489, start_index=371, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab7b%20is%20a%20small%20GTPase,16')
2. AnnotationURLCitation(end_index=695, start_index=577, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab7b%20is%20a%20small%20GTPase,16')
3. AnnotationURLCitation(end_index=839, start_index=696, title='Evidence for Rab7b and Its Splice Isoforms Having Distinct Biological Functions from Rab7a', type='url_citation', url='https://www.mdpi.com/1422-0067/26/6/2610#:~:text=The%20protein%20sequences%20of%20Rab7a,alignments%20of%20Rab7a%20and%20Rab7b')
4. AnnotationURLCitation(end_index=1212, start_index=1031, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=regulating%20the%20trafficking%20between%20the,effectors%3A%20motor%20proteins%20that%20transport')
5. AnnotationURLCitation(end_index=1655, start_index=1486, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=a%20recently%20identified%20Rab%20protein,like%20Receptors%20%28TLRs%29%20and%20other')
6. AnnotationURLCitation(end_index=1782, start_index=1656, title='Evidence for Rab7b and Its Splice Isoforms Having Distinct Biological Functions from Rab7a', type='url_citation', url='https://www.mdpi.com/1422-0067/26/6/2610#:~:text=mitochondria%20,lysosomes%2C%20evidence%20that%20Rab7a%20is')
7. AnnotationURLCitation(end_index=2016, start_index=1883, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=knockdown%20of%20Rab7B%20,Here%2C%20we%20present')
8. AnnotationURLCitation(end_index=2582, start_index=2429, title='Rab7b controls trafficking from endosomes to the TGN - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/20375062/#:~:text=degradation%20of%20TLR4%20and%20TLR9,of%20the%20late%20endosomal%20markers')
9. AnnotationURLCitation(end_index=2913, start_index=2760, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab%20proteins%20are%20key,receptors%2C%20opening%20for%20a%20revised')
10. AnnotationURLCitation(end_index=3196, start_index=3053, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab7%20regulates%20the%20transport%20to,organizing%20center')
11. AnnotationURLCitation(end_index=3577, start_index=3424, title='Rab7b controls trafficking from endosomes to the TGN - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/20375062/#:~:text=degradation%20of%20TLR4%20and%20TLR9,of%20the%20late%20endosomal%20markers')
12. AnnotationURLCitation(end_index=4098, start_index=3917, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=regulating%20the%20trafficking%20between%20the,effectors%3A%20motor%20proteins%20that%20transport')
13. AnnotationURLCitation(end_index=4468, start_index=4293, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=laboratories%20demonstrate%20that%20Rab7b%20does,differences%20between%20Rab7%20and%20Rab7b')
14. AnnotationURLCitation(end_index=4787, start_index=4612, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=laboratories%20demonstrate%20that%20Rab7b%20does,differences%20between%20Rab7%20and%20Rab7b')
15. AnnotationURLCitation(end_index=5126, start_index=4954, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=Recently%2C%20we%20identified%20the%20actin,depleted%20by%20siRNA%2C%20indicating%20that')
16. AnnotationURLCitation(end_index=5271, start_index=5127, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=and%20polarity.,actin%20filaments%20and%20therefore%20stress')
17. AnnotationURLCitation(end_index=5727, start_index=5573, title='Rab7b controls trafficking from endosomes to the TGN - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/20375062/#:~:text=Depletion%20of%20Rab7b%20or%20expression,that%20Rab7b%20is%20required%20for')
18. AnnotationURLCitation(end_index=6106, start_index=5952, title='Rab7b controls trafficking from endosomes to the TGN - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/20375062/#:~:text=Depletion%20of%20Rab7b%20or%20expression,that%20Rab7b%20is%20required%20for')
19. AnnotationURLCitation(end_index=6451, start_index=6297, title='Rab7b controls trafficking from endosomes to the TGN - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/20375062/#:~:text=Depletion%20of%20Rab7b%20or%20expression,that%20Rab7b%20is%20required%20for')
20. AnnotationURLCitation(end_index=6834, start_index=6711, title='Rab7b controls trafficking from endosomes to the TGN - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/20375062/#:~:text=whereas%20an%20activated%2C%20GTP,expressing')
21. AnnotationURLCitation(end_index=7157, start_index=7029, title='Rab7b controls trafficking from endosomes to the TGN - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/20375062/#:~:text=hexosaminidase,that%20Rab7b%20is%20required%20for')
22. AnnotationURLCitation(end_index=7327, start_index=7158, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=controls%20however%20vesicular%20trafficking%20from,TLRs%29%20and%20other%20receptors')
23. AnnotationURLCitation(end_index=7802, start_index=7659, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab7%20regulates%20the%20transport%20to,organizing%20center')
24. AnnotationURLCitation(end_index=8229, start_index=8060, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=controls%20however%20vesicular%20trafficking%20from,TLRs%29%20and%20other%20receptors')
25. AnnotationURLCitation(end_index=8376, start_index=8230, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=match%20at%20L88%20mammalian%20cells.,26%7D%20We%20previously')
26. AnnotationURLCitation(end_index=8656, start_index=8537, title='Rab7b controls trafficking from endosomes to the TGN - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/20375062/#:~:text=degradation%20of%20TLR4%20and%20TLR9,MPR')
27. AnnotationURLCitation(end_index=8926, start_index=8757, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=controls%20however%20vesicular%20trafficking%20from,TLRs%29%20and%20other%20receptors')
28. AnnotationURLCitation(end_index=9217, start_index=9048, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=a%20recently%20identified%20Rab%20protein,like%20Receptors%20%28TLRs%29%20and%20other')
29. AnnotationURLCitation(end_index=9633, start_index=9458, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=laboratories%20demonstrate%20that%20Rab7b%20does,differences%20between%20Rab7%20and%20Rab7b')
30. AnnotationURLCitation(end_index=9948, start_index=9776, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=Recently%2C%20we%20identified%20the%20actin,depleted%20by%20siRNA%2C%20indicating%20that')
31. AnnotationURLCitation(end_index=10478, start_index=10309, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=controls%20however%20vesicular%20trafficking%20from,TLRs%29%20and%20other%20receptors')
32. AnnotationURLCitation(end_index=11207, start_index=11054, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab%20proteins%20are%20key,receptors%2C%20opening%20for%20a%20revised')
33. AnnotationURLCitation(end_index=11299, start_index=11208, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=,066027')
34. AnnotationURLCitation(end_index=11600, start_index=11509, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=,066027')
35. AnnotationURLCitation(end_index=11898, start_index=11807, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=,066027')
36. AnnotationURLCitation(end_index=12442, start_index=12318, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=lysosomal%20degradation%20of%20TLR4,triggered')
37. AnnotationURLCitation(end_index=12828, start_index=12666, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=us%20before%2C%20which%20is%20mainly,macrophages%20by%20impairing%20activation%20of')
38. AnnotationURLCitation(end_index=13186, start_index=13032, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=expression%20of%20the%20TLR9%20in,via%20promotion%20of%20TLR9%20degradation')
39. AnnotationURLCitation(end_index=13458, start_index=13304, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=expression%20of%20the%20TLR9%20in,via%20promotion%20of%20TLR9%20degradation')
40. AnnotationURLCitation(end_index=13990, start_index=13811, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=Inappropriate%20activation%20of%20TLR9%20has,small%20guanosine%20triphosphatase%2C%20identified%20by')
41. AnnotationURLCitation(end_index=14343, start_index=14164, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=Inappropriate%20activation%20of%20TLR9%20has,small%20guanosine%20triphosphatase%2C%20identified%20by')
42. AnnotationURLCitation(end_index=14498, start_index=14344, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=expression%20of%20the%20TLR9%20in,via%20promotion%20of%20TLR9%20degradation')
43. AnnotationURLCitation(end_index=15015, start_index=14897, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab7b%20is%20a%20small%20GTPase,16')
44. AnnotationURLCitation(end_index=15367, start_index=15224, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=monocytes%20%28CD14%5E%7B%2B%7D%20cells%29%2C%20monocyte,23')
45. AnnotationURLCitation(end_index=15711, start_index=15557, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=expression%20of%20the%20TLR9%20in,via%20promotion%20of%20TLR9%20degradation')
46. AnnotationURLCitation(end_index=16100, start_index=15961, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=,PLoS%20One%202014%3B%209%3Ae85833%3B%20PMID%3A24489676')
47. AnnotationURLCitation(end_index=16555, start_index=16412, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab7%20regulates%20the%20transport%20to,organizing%20center')
48. AnnotationURLCitation(end_index=17004, start_index=16835, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=a%20recently%20identified%20Rab%20protein,like%20Receptors%20%28TLRs%29%20and%20other')
49. AnnotationURLCitation(end_index=17794, start_index=17622, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=Recently%2C%20we%20identified%20the%20actin,depleted%20by%20siRNA%2C%20indicating%20that')
50. AnnotationURLCitation(end_index=17959, start_index=17795, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=interacts%20directly%20with%20the%20actin,and%20thereby%20for%20cell%20migration')
51. AnnotationURLCitation(end_index=18291, start_index=18119, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=Recently%2C%20we%20identified%20the%20actin,depleted%20by%20siRNA%2C%20indicating%20that')
52. AnnotationURLCitation(end_index=18665, start_index=18493, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=Recently%2C%20we%20identified%20the%20actin,depleted%20by%20siRNA%2C%20indicating%20that')
53. AnnotationURLCitation(end_index=19204, start_index=19037, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=Myosin%20II%20interacts%20with%20actin,actin%20filaments%20and%20therefore%20stress')
54. AnnotationURLCitation(end_index=19365, start_index=19205, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=which%20causes%20myosin%20II%20to,RhoA%20activation%2C%20can%20control%20MLC')
55. AnnotationURLCitation(end_index=19745, start_index=19602, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=responsible%20for%20the%20phosphorylation%20of,15%7D%20When')
56. AnnotationURLCitation(end_index=20278, start_index=20111, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=Myosin%20II%20interacts%20with%20actin,actin%20filaments%20and%20therefore%20stress')
57. AnnotationURLCitation(end_index=20439, start_index=20279, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=which%20causes%20myosin%20II%20to,RhoA%20activation%2C%20can%20control%20MLC')
58. AnnotationURLCitation(end_index=21224, start_index=21073, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=required%20for%20fast%20DC%20migration,first%20author%20of%20the%20paper')
59. AnnotationURLCitation(end_index=21390, start_index=21225, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=previously%20identified%20myosin%20II%20as,we%20demonstrate%20that%20Rab7b%20interacts')
60. AnnotationURLCitation(end_index=21683, start_index=21527, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=Rab7b%20reduces%20myosin%20II%20light,Person%20interview%20with%20the%20first')
61. AnnotationURLCitation(end_index=22082, start_index=21919, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=Lysosomal%20signaling%20facilitates%20the%20migration,found%20that%20the%20lack%20of')
62. AnnotationURLCitation(end_index=22248, start_index=22083, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=required%20for%20fast%20DC%20migration,immune%20cell%20migration%20through%20lysosomal')
63. AnnotationURLCitation(end_index=22701, start_index=22527, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=that%20transport%20antigens%20from%20peripheral,immune%20cell%20migration%20through%20lysosomal')
64. AnnotationURLCitation(end_index=22951, start_index=22786, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=previously%20identified%20myosin%20II%20as,we%20demonstrate%20that%20Rab7b%20interacts')
65. AnnotationURLCitation(end_index=23785, start_index=23618, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=Myosin%20II%20interacts%20with%20actin,actin%20filaments%20and%20therefore%20stress')
66. AnnotationURLCitation(end_index=23942, start_index=23786, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=Rab7b%20reduces%20myosin%20II%20light,Person%20interview%20with%20the%20first')
67. AnnotationURLCitation(end_index=24420, start_index=24258, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=Rab%20proteins%20are%20small%20GTPases,important%20for%20the%20remodeling%20of')
68. AnnotationURLCitation(end_index=24586, start_index=24421, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=the%20proper%20trafficking%20of%20several,for%20Rab%20proteins%2C%20in%20addition')
69. AnnotationURLCitation(end_index=25226, start_index=25108, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab7b%20is%20a%20small%20GTPase,16')
70. AnnotationURLCitation(end_index=25511, start_index=25368, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=monocytes%20%28CD14%5E%7B%2B%7D%20cells%29%2C%20monocyte,23')
71. AnnotationURLCitation(end_index=25884, start_index=25741, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=monocytes%20%28CD14%5E%7B%2B%7D%20cells%29%2C%20monocyte,23')
72. AnnotationURLCitation(end_index=26377, start_index=26234, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=monocytes%20%28CD14%5E%7B%2B%7D%20cells%29%2C%20monocyte,23')
73. AnnotationURLCitation(end_index=26851, start_index=26709, title='Evidence for Rab7b and Its Splice Isoforms Having Distinct Biological Functions from Rab7a', type='url_citation', url='https://www.mdpi.com/1422-0067/26/6/2610#:~:text=Two%20splice%20isoforms%20of%20Rab7b,splice%20isoforms%20is%20specific%20to')
74. AnnotationURLCitation(end_index=27001, start_index=26852, title='Evidence for Rab7b and Its Splice Isoforms Having Distinct Biological Functions from Rab7a', type='url_citation', url='https://www.mdpi.com/1422-0067/26/6/2610#:~:text=articles%20demonstrate%20the%20role%20of,the%20Rab7%20homologues%20are%20different')
75. AnnotationURLCitation(end_index=27552, start_index=27390, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=us%20before%2C%20which%20is%20mainly,macrophages%20by%20impairing%20activation%20of')
76. AnnotationURLCitation(end_index=28507, start_index=28353, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=expression%20of%20the%20TLR9%20in,via%20promotion%20of%20TLR9%20degradation')
77. AnnotationURLCitation(end_index=28888, start_index=28709, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=Inappropriate%20activation%20of%20TLR9%20has,small%20guanosine%20triphosphatase%2C%20identified%20by')
78. AnnotationURLCitation(end_index=29043, start_index=28889, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=expression%20of%20the%20TLR9%20in,via%20promotion%20of%20TLR9%20degradation')
79. AnnotationURLCitation(end_index=29401, start_index=29262, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=,PLoS%20One%202014%3B%209%3Ae85833%3B%20PMID%3A24489676')
80. AnnotationURLCitation(end_index=30058, start_index=29889, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=controls%20however%20vesicular%20trafficking%20from,TLRs%29%20and%20other%20receptors')
81. AnnotationURLCitation(end_index=30543, start_index=30392, title='Evidence for Rab7b and Its Splice Isoforms Having Distinct Biological Functions from Rab7a', type='url_citation', url='https://www.mdpi.com/1422-0067/26/6/2610#:~:text=match%20at%20L175%20articles%20demonstrate,the%20Rab7%20homologues%20are%20different')
82. AnnotationURLCitation(end_index=31130, start_index=30965, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=previously%20identified%20myosin%20II%20as,we%20demonstrate%20that%20Rab7b%20interacts')
83. AnnotationURLCitation(end_index=32222, start_index=32039, title='Rab7B/42 Is Functionally Involved in Protein Degradation on Melanosomes in Keratinocytes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10739166/#:~:text=Our%20findings%20indicated%20that%20Rab7B%2F42,degradation%20on%20melanosomes%20in%20keratinocytes')
84. AnnotationURLCitation(end_index=32324, start_index=32223, title='Rab7B/42 Is Functionally Involved in Protein Degradation on Melanosomes in Keratinocytes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10739166/#:~:text=each%20Rab,Golgi')
85. AnnotationURLCitation(end_index=32648, start_index=32473, title='Rab7B/42 Is Functionally Involved in Protein Degradation on Melanosomes in Keratinocytes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10739166/#:~:text=identified%20as%20Rab42%3B%20Itoh%20et,degradation%20on%20melanosomes%20in%20keratinocytes')
86. AnnotationURLCitation(end_index=32780, start_index=32649, title='Rab7B/42 Is Functionally Involved in Protein Degradation on Melanosomes in Keratinocytes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10739166/#:~:text=match%20at%20L427%20Rab7B%2F42%20KD,KO%20cells')
87. AnnotationURLCitation(end_index=33563, start_index=33430, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=knockdown%20of%20Rab7B%20,Here%2C%20we%20present')
88. AnnotationURLCitation(end_index=33722, start_index=33564, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=highlight%20the%20unique%20role%20of,part%2C%20at%20the%20molecular%20and')
89. AnnotationURLCitation(end_index=34072, start_index=33911, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=be%20restored%20by%20knockdown%20of,positive%20organelles.%20These%20results')
90. AnnotationURLCitation(end_index=34411, start_index=34250, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=be%20restored%20by%20knockdown%20of,positive%20organelles.%20These%20results')
91. AnnotationURLCitation(end_index=34580, start_index=34412, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=findings%20suggest%20that%20Rab7B%20could,the%20molecular%20and%20cellular%20levels')
92. AnnotationURLCitation(end_index=34900, start_index=34708, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=next%20step%2C%20we%20analyzed%20the,to%20incompletely%20differentiated%2C%20undifferentiated%2C%20and%2For')
93. AnnotationURLCitation(end_index=35060, start_index=34901, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=Effects%20of%20Rab7B%20knockdown%20on,like%20widespread%20membranes%20were')
94. AnnotationURLCitation(end_index=35563, start_index=35402, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=be%20restored%20by%20knockdown%20of,positive%20organelles.%20These%20results')
95. AnnotationURLCitation(end_index=35723, start_index=35564, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=To%20test%20the%20possibility%20that,A243V%20mutation%20in%20an%20isotonic')
96. AnnotationURLCitation(end_index=36182, start_index=36049, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=knockdown%20of%20Rab7B%20,Here%2C%20we%20present')
97. AnnotationURLCitation(end_index=36351, start_index=36183, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=findings%20suggest%20that%20Rab7B%20could,the%20molecular%20and%20cellular%20levels')
98. AnnotationURLCitation(end_index=37045, start_index=36876, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=a%20recently%20identified%20Rab%20protein,like%20Receptors%20%28TLRs%29%20and%20other')
99. AnnotationURLCitation(end_index=37411, start_index=37252, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=enzymes%20delivery%20to%20lysosomes%20and,TLRs%29%20and%20other%20receptors')
100. AnnotationURLCitation(end_index=37774, start_index=37612, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=Rab%20proteins%20are%20small%20GTPases,important%20for%20the%20remodeling%20of')
101. AnnotationURLCitation(end_index=37935, start_index=37775, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=which%20causes%20myosin%20II%20to,RhoA%20activation%2C%20can%20control%20MLC')
102. AnnotationURLCitation(end_index=38296, start_index=38132, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=from%20late%20endosomes%20toward%20the,that%20Rab7b%20can%20control%20actomyosin')
103. AnnotationURLCitation(end_index=38462, start_index=38297, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=required%20for%20fast%20DC%20migration,immune%20cell%20migration%20through%20lysosomal')
104. AnnotationURLCitation(end_index=39974, start_index=39823, title='Evidence for Rab7b and Its Splice Isoforms Having Distinct Biological Functions from Rab7a', type='url_citation', url='https://www.mdpi.com/1422-0067/26/6/2610#:~:text=match%20at%20L175%20articles%20demonstrate,the%20Rab7%20homologues%20are%20different')
105. AnnotationURLCitation(end_index=40403, start_index=40285, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab7b%20is%20a%20small%20GTPase,16')
106. AnnotationURLCitation(end_index=40625, start_index=40534, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=,066027')
107. AnnotationURLCitation(end_index=40883, start_index=40729, title='Late endosome/lysosome-localized Rab7b suppresses TLR9-initiated proinflammatory cytokine and type I IFN production in macrophages - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/19587007/#:~:text=expression%20of%20the%20TLR9%20in,via%20promotion%20of%20TLR9%20degradation')
108. AnnotationURLCitation(end_index=41151, start_index=40997, title='Rab7b controls trafficking from endosomes to the TGN - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/20375062/#:~:text=Depletion%20of%20Rab7b%20or%20expression,that%20Rab7b%20is%20required%20for')
109. AnnotationURLCitation(end_index=41408, start_index=41255, title='Rab7b and receptors trafficking - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2974065/#:~:text=Rab%20proteins%20are%20key,receptors%2C%20opening%20for%20a%20revised')
110. AnnotationURLCitation(end_index=41682, start_index=41539, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=responsible%20for%20the%20phosphorylation%20of,15%7D%20When')
111. AnnotationURLCitation(end_index=41788, start_index=41683, title='Rab7b at the intersection of intracellular trafficking and cell migration - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4802807/#:~:text=,PMC%20free%20article')
112. AnnotationURLCitation(end_index=42075, start_index=41892, title='Rab7B/42 Is Functionally Involved in Protein Degradation on Melanosomes in Keratinocytes - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10739166/#:~:text=Our%20findings%20indicated%20that%20Rab7B%2F42,degradation%20on%20melanosomes%20in%20keratinocytes')
113. AnnotationURLCitation(end_index=42373, start_index=42199, title='Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34494097/#:~:text=that%20transport%20antigens%20from%20peripheral,immune%20cell%20migration%20through%20lysosomal')
114. AnnotationURLCitation(end_index=42629, start_index=42496, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=knockdown%20of%20Rab7B%20,Here%2C%20we%20present')
115. AnnotationURLCitation(end_index=42791, start_index=42630, title='CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11402064/#:~:text=be%20restored%20by%20knockdown%20of,positive%20organelles.%20These%20results')