rab-7 (W03C9.3) encodes the single C. elegans ortholog of the Rab7 small GTPase, a 209-residue Rab-family protein with the conserved switch I and switch II regions and a C-terminal prenylation motif. Like other Rabs it acts as a membrane-associated molecular switch that cycles between GDP- and GTP-bound states; its intrinsic GTP hydrolysis is stimulated by the TBC-domain GAPs RBG-3 and TBC-2, and its activation and recruitment to maturing endosomes at the early-to-late endosome transition depend on SAND-1/Mon1. RAB-7 marks late endosomes and lysosomes in the intestine, coelomocytes and oocytes, and is recruited to phagosomes containing apoptotic cell corpses shortly after phosphatidylinositol 3-phosphate appears on them. It is required for endocytic cargo (yolk, fluid-phase markers) to progress from early endosomes to late endosomes and lysosomes, and for the recruitment and fusion of lysosomes with phagosomes during apoptotic cell corpse degradation, downstream of the CED-1 engulfment receptor pathway. On lysosomes it recruits the HEAT-repeat lysosome scission factor HPO-27. Maternal and zygotic loss of rab-7 causes embryonic lethality and persistent cell corpses.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001555 oocyte growth | IMP PMID:10588660 Receptor-mediated endocytosis in the Caenorhabditis elegans ... | MARK AS OVER ANNOTATED | Summary: Grant and Hirsh used RNAi against Ce-rab7 in a YP170::GFP yolk-uptake assay. The text reports that rab-7 RNAi did not significantly impair yolk uptake into oocytes but mislocalized yolk into enlarged peripheral vesicles, consistent with a block in a late endocytic step. Reason: The paper's own description of the rab-7 RNAi phenotype is a defect in endosomal trafficking of internalized yolk, not a defect in oocyte growth: uptake itself was not significantly impaired. Any effect on oocyte size would be an indirect consequence of the general endolysosomal trafficking defect. The contents of Table 1 are not in the cached text, so the row is marked over-annotated rather than removed. Supporting Evidence: PMID:10588660 Although Ce-rab7 (RNAi) did not appear to significantly impair the uptake of YP170::GFP into oocytes, YP170::GFP was mislocalized in them |
| GO:0003924 GTPase activity | IDA PMID:17762880 An endocytic pathway as a target of tubby for regulation of ... | MODIFY | Summary: RBG-3, a Rab GAP that interacts with TUB-1, stimulates the intrinsic GTPase activity of C. elegans RAB-7 in vitro. Reason: A GAP-stimulated GTP hydrolysis assay on RAB-7 directly demonstrates that RAB-7 has intrinsic GTPase activity. This is the core molecular activity of a Rab switch. The term is correct but general; it is refined to its is_a child G protein activity (GO:0003925), the informative MF for a Rab GTPase switch. Proposed replacements: G protein activity Supporting Evidence: PMID:17762880 We found that RBG-3 preferentially stimulates the intrinsic GTPase activity of RAB-7 in both human and C. elegans |
| GO:0003924 GTPase activity | IDA PMID:20462958 TBC-2 regulates RAB-5/RAB-7-mediated endosomal trafficking i... | MODIFY | Summary: A real-time optical GTPase assay showed GTP hydrolysis by recombinant RAB-7, which is accelerated by TBC-2 (more weakly than for RAB-5). Reason: Direct biochemical demonstration of GTP hydrolysis by RAB-7, intrinsic and GAP-stimulated. Consistent with the other IDA row and with Rab-family membership. The term is correct but general; it is refined to its is_a child G protein activity (GO:0003925), the informative MF for a Rab GTPase switch. Proposed replacements: G protein activity Supporting Evidence: PMID:20462958 Using an in vitro GAP assay that measures GTP hydrolysis in real-time, we show that TBC-2 specifically catalyzes GTP hydrolysis by RAB-5 and to a lesser extent RAB-7. |
| GO:0003924 GTPase activity | IEA GO_REF:0000120 | MODIFY | Summary: Electronic annotation from the small GTPase domain (IPR001806) and a UniRule; RAB-7 is a member of the Rab family of small GTPases. Reason: Correct family-based inference, confirmed experimentally by two IDA rows (PMID:17762880, PMID:20462958). The term is correct but general; it is refined to its is_a child G protein activity (GO:0003925), the informative MF for a Rab GTPase switch. Proposed replacements: G protein activity Supporting Evidence: file:worm/rab-7/rab-7-uniprot.txt Belongs to the small GTPase superfamily. Rab family. PMID:20462958 we show that TBC-2 specifically catalyzes GTP hydrolysis by RAB-5 and to a lesser extent RAB-7 |
| GO:0005525 GTP binding | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation from small GTPase domain signatures. The GTP-binding-deficient T23N mutant of RAB-7 fails to rescue rab-7(ok511) and fails to localize to phagosomes, showing that guanine nucleotide binding is needed for function. Reason: GTP binding is an intrinsic property of every functional Rab and is supported in this gene by the T23N mutant analysis. It is a component of, not a substitute for, the GTPase switch activity. Supporting Evidence: PMID:18351800 The transgene Pced-1gfp::rab-7(T23N) did not rescue the Ded phenotype in rab-7(ok511) mutants (Figure 5A), indicating that GTP binding is essential for RAB-7 function. |
| GO:0005764 lysosome | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference from the Rab7 clade node PTN000635769, seeded by human RAB7A, fly Rab7, mouse/rat Rab7 and C. elegans rab-7 itself. Reason: Checked per the organelle policy: the IBA stops at the organelle because the seeding evidence is mostly organelle co-staining. The claim holds for C. elegans RAB-7, which labels LMP-1-positive lysosomes in the intestine (PMID:16801682) and is recruited to lysosomes where it recruits HPO-27 (PMID:38538795). The membrane sub-compartment is already captured by the GO:0005765 lysosomal membrane row. Supporting Evidence: PMID:16801682 RAB-7 labels not only late endosomes but also lysosomes |
| GO:0005764 lysosome | IDA PMID:16801682 The phosphoinositide kinase PIKfyve/Fab1p regulates terminal... | ACCEPT | Summary: In the intestine, GFP/RFP::RAB-7 decorates vacuoles that accumulate fluid-phase Texas-Red BSA after a long chase and are LMP-1-positive, i.e. lysosomes as well as late endosomes. Reason: Direct co-localization evidence from whole-organelle co-staining that cannot resolve the sub-compartment; ACCEPT under the organelle policy. Supporting Evidence: PMID:16801682 RAB-7 labels not only late endosomes but also lysosomes |
| GO:0005764 lysosome | IDA PMID:20921409 Sequential action of Caenorhabditis elegans Rab GTPases regu... | ACCEPT | Summary: Guo et al. (abstract-only cache) analysed RAB-7 together with RAB-14 and UNC-108 in phagolysosome formation; the abstract states that RAB-7 mediates fusion of lysosomes to phagosomes. Reason: The localization data are in the full text, which is not cached; the claim is consistent with the independent IDA from PMID:16801682 and with RAB-7's role in lysosome fusion, so the curator's experimental annotation is accepted. Supporting Evidence: PMID:20921409 RAB-14 and UNC-108 recruit lysosomes, whereas RAB-7 mediates fusion of lysosomes to phagosomes |
| GO:0005765 lysosomal membrane | IDA PMID:38538795 The HEAT repeat protein HPO-27 is a lysosome fission factor. | ACCEPT | Summary: HPO-27, a lysosome scission factor, is recruited to lysosomes by RAB-7 (abstract-only cache); RAB-7 is therefore active on the lysosome surface. Reason: As a prenylated Rab, RAB-7 associates with the cytosolic face of the lysosomal membrane, where it recruits effectors. The sub-compartment is supported by two lines (prenylation-dependent membrane anchoring typical of Rabs and effector recruitment to lysosomes). Full text not cached; curator's IDA is accepted. Supporting Evidence: PMID:38538795 recruited to lysosomes by RAB-7 and enriched at scission sites |
| GO:0005770 late endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of late endosome location from the Rab7 clade, consistent with direct observations of RAB-7 on late endosomes in C. elegans. Reason: Late endosome localization is the defining feature of Rab7 across eukaryotes and is directly shown for worm RAB-7 (PMID:16801682, PMID:26783301, PMID:23840591). Supporting Evidence: PMID:23840591 RAB-7-positive late endosomes were more abundant |
| GO:0005770 late endosome | IDA PMID:19915558 AMPH-1/Amphiphysin/Bin1 functions with RME-1/Ehd1 in endocyt... | ACCEPT | Summary: GFP-RAB-7 was used as the late endosome marker in the intestine in a study of AMPH-1; AMPH-1 did not co-localize with it. Reason: Use of GFP-RAB-7 as an established late endosome marker in this paper reflects the earlier direct localization; the claim is correct. Supporting Evidence: PMID:19915558 late endosome (GFP-RAB-7) |
| GO:0008333 endosome to lysosome transport | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that Rab7 orthologs act in transport of cargo from late endosomes to lysosomes, matching C. elegans data. Reason: In C. elegans, RAB-7 acts in endosome to lysosome traffic; rab-7 RNAi blocks a late transport step for yolk in oocytes, and RAB-7 function at lysosomes is distinct from its SAND-1-dependent function at the early-to-late transition. Core process. Supporting Evidence: PMID:17203072 The small rab-GTPase RAB-7 acts in endosome and endosome to lysosome traffic |
| GO:0010171 body morphogenesis | IMP PMID:10588660 Receptor-mediated endocytosis in the Caenorhabditis elegans ... | MARK AS OVER ANNOTATED | Summary: Progeny of rab-7(RNAi) hermaphrodites were mildly dumpy (Dpy). Reason: A mild Dpy body-shape phenotype after RNAi is a pleiotropic, indirect consequence of a general endolysosomal trafficking defect; nothing indicates that RAB-7 does any of the work of body morphogenesis. Supporting Evidence: PMID:10588660 Larvae and adult progeny of Ce-rab7 (RNAi) worms appeared mildly Dpy. |
| GO:0016197 endosomal transport | IMP PMID:10588660 Receptor-mediated endocytosis in the Caenorhabditis elegans ... | MODIFY | Summary: rab-7 RNAi causes internalized YP170::GFP to accumulate in large peripheral vesicles of oocytes, resembling the block in early-to-late endosome transport caused by dominant-negative Rab7 in mammalian cells. Reason: Correct but general. The evidence and the wider literature support the two more specific endosomal transport steps in which RAB-7 acts: early endosome to late endosome transport and endosome to lysosome transport (the latter already carried by the IBA row). Proposed replacements: early endosome to late endosome transport endosome to lysosome transport Supporting Evidence: PMID:10588660 We have blocked expression of Ce-rab7 by RNAi and observed accumulation of YP170::GFP in large peripheral vesicles of the oocyte, a phenotype very similar to that described above for mammalian cells PMID:17203072 The small rab-GTPase RAB-7 acts in endosome and endosome to lysosome traffic |
| GO:0030670 phagocytic vesicle membrane | IDA PMID:18351800 Phagocytic receptor CED-1 initiates a signaling pathway for ... | ACCEPT | Summary: Time-lapse imaging shows functional GFP::RAB-7 recruited to the surface of phagosomes containing apoptotic cells about 3 min after PI(3)P appears, and persisting until the corpse is degraded. Reason: Direct, well-controlled localization of a rescuing GFP::RAB-7 fusion to the phagosome surface, where RAB-7 acts to drive lysosome fusion. Supporting Evidence: PMID:18351800 RAB-7 was recruited to the surface of a phagosome approximately 3 min after PI(3)P appeared on the same phagosome |
| GO:0031090 organelle membrane | IDA PMID:17203072 Caenorhabditis elegans SAND-1 is essential for RAB-7 functio... | MODIFY | Summary: Poteryaev et al. (abstract-only cache) examined RAB-7 membrane association in the presence and absence of SAND-1, which is required for RAB-7 function at the early-to-late endosome transition. Reason: Organelle membrane is correct but uninformatively general. The membranes RAB-7 associates with in this and other worm studies are late endosome and lysosome membranes; GO:0031902 late endosome membrane is already carried by the gene. Proposed replacements: late endosome membrane Supporting Evidence: PMID:17203072 SAND-1 is essential for RAB-7 function at the transition from early to late endosomes, but not for RAB-7 function at lysosomes |
| GO:0031902 late endosome membrane | IDA PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | ACCEPT | Summary: mCherry::RAB-7 is progressively recruited to maturing endosomes in coelomocytes as PtdIns3P declines, marking early-to-late endosome conversion. Reason: Direct live imaging of RAB-7 acquisition on endosome membranes during conversion to late endosomes. Supporting Evidence: PMID:26783301 Thus, conversion of early to late endosomes is marked by a strong decrease or turnover of endosomal PtdIns3P and appearance of RAB-7. |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Mapping from the UniProt subcellular location "Late endosome membrane", which in this unreviewed entry is an ARBA prediction. Reason: Although the UniProt source is a rule-based prediction, the claim is independently supported by direct imaging of RAB-7 on maturing endosomes (PMID:26783301). Supporting Evidence: PMID:26783301 In N2 coelomocytes, the progressive disappearance of RAB-5 and enrichment of RAB-7 on endosomes normally occurred within |
| GO:0045335 phagocytic vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of phagosome localization for Rab7 orthologs, consistent with direct observation in C. elegans. Reason: Worm RAB-7 is enriched on phagosomes containing apoptotic cells (PMID:18351800); the more specific membrane term is carried by the IDA row. Supporting Evidence: PMID:18351800 These results indicate that both PI(3)P and RAB-7 are enriched on the surface of all phagosomes |
| GO:0045335 phagocytic vesicle | IDA PMID:20921409 Sequential action of Caenorhabditis elegans Rab GTPases regu... | ACCEPT | Summary: Guo et al. (abstract-only cache) followed RAB-7 together with RAB-14 and UNC-108 on phagosomes containing apoptotic cells. Reason: Consistent with direct imaging in PMID:18351800; curator's IDA from the full text is accepted. Supporting Evidence: PMID:20921409 Three Rabs, RAB-14, UNC-108/RAB2, and RAB-7, act in sequential steps to control phagolysosome formation. |
| GO:0048284 organelle fusion | IGI PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | MODIFY | Summary: Genetic interactions between rab-7 and sorf-1/sorf-2 affect endosome fusion: in sorf mutants, loss of rab-7 (or dominant-negative RAB-7(T23N)) leads to persistent PtdIns3P and continuous fusion of early endosomes into giant endosomes. Reason: RAB-7 does take part in organelle fusion, but organelle fusion is too general. The fusion step that RAB-7 is directly shown to drive in C. elegans is fusion of lysosomes with phagosomes (PMID:18351800, PMID:20921409), already carried as GO:0090385. The IGI data in this paper are themselves indirect (loss of rab-7 increases early endosome fusion in sorf mutants through persistent PtdIns3P), so they do not support a more specific endosome fusion term on their own. Proposed replacements: phagosome-lysosome fusion Supporting Evidence: PMID:26783301 In sorf-1(tm3855) and sorf-2(tm5210) animals, however, heat shock–induced RAB-7(T23N) expression caused continuous fusion of 2xFYVE::GFP-positive endosomes into a giant endosome PMID:18351800 whose function is essential for promoting the recruitment and fusion of lysosomes to phagosomes |
| GO:0048284 organelle fusion | IGI PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | MODIFY | Summary: Same genetic-interaction data as the sibling row, with a different partner pair. Reason: As for the sibling rows: organelle fusion is correct but general; the specific fusion step RAB-7 drives is phagosome-lysosome fusion. Proposed replacements: phagosome-lysosome fusion Supporting Evidence: PMID:18351800 whose function is essential for promoting the recruitment and fusion of lysosomes to phagosomes |
| GO:0048284 organelle fusion | IGI PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | MODIFY | Summary: Same genetic-interaction data as the sibling rows, with a different partner pair. Reason: As for the sibling rows: organelle fusion is correct but general; the specific fusion step RAB-7 drives is phagosome-lysosome fusion. Proposed replacements: phagosome-lysosome fusion Supporting Evidence: PMID:20921409 RAB-14 and UNC-108 recruit lysosomes, whereas RAB-7 mediates fusion of lysosomes to phagosomes |
| GO:0061462 protein localization to lysosome | IDA PMID:38538795 The HEAT repeat protein HPO-27 is a lysosome fission factor. | KEEP AS NON CORE | Summary: RAB-7 is required to recruit the lysosome scission factor HPO-27 (and its human homologue MROH1) to lysosomes (abstract-only cache). Reason: Effector recruitment to the lysosome surface is a genuine, direct consequence of active RAB-7, and the curator's IDA from the full text is accepted. It is one instance of the general Rab effector-recruitment mechanism rather than a distinct core function. Supporting Evidence: PMID:38538795 recruited to lysosomes by RAB-7 and enriched at scission sites |
| GO:0090385 phagosome-lysosome fusion | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference from human RAB7A at the Rab7 clade node; directly supported in C. elegans. Reason: RAB-7 is essential for recruitment and fusion of lysosomes with phagosomes containing apoptotic cells (PMID:18351800) and acts after RAB-14/UNC-108 at the fusion step (PMID:20921409). Core process. Supporting Evidence: PMID:18351800 We further elucidate that the signaling pathway led by CED-1 promotes phagolysosome formation through activating RAB-7, whose function is essential for promoting the recruitment and fusion of lysosomes to phagosomes. |
| GO:0090387 phagolysosome assembly involved in apoptotic cell clearance | IMP PMID:20921409 Sequential action of Caenorhabditis elegans Rab GTPases regu... | ACCEPT | Summary: Loss of rab-7 blocks fusion of lysosomes with phagosomes containing apoptotic cells; RAB-7 acts at the fusion step after RAB-14 and UNC-108 recruit lysosomes. Reason: Directly supported in two independent studies (PMID:20921409 abstract; PMID:18351800 full text, where rab-7(ok511) phagosomes persist and fail to acquire lysosomal CTNS-1 particles). RAB-7 does the work of the fusion step as the membrane-bound switch that recruits the fusion machinery. Supporting Evidence: PMID:20921409 RAB-14 and UNC-108 recruit lysosomes, whereas RAB-7 mediates fusion of lysosomes to phagosomes PMID:18351800 In wild-type embryos, phagosomes disappeared within a period of 30–70 min after their formation; in rab-7(ok511) embryos, ten phagosomes monitored all lasted much longer than 90 min |
| GO:2000643 positive regulation of early endosome to late endosome transport | IGI PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | MODIFY | Summary: rab-7 genetically interacts with sorf-1/sorf-2 in PtdIns3P turnover during early-to-late endosome conversion; RAB-7 is recruited to maturing endosomes as the conversion proceeds. Reason: RAB-7 is not an upstream regulator of early-to-late endosome transport; it is the Rab that defines the late compartment and is itself a core participant in the Rab5-to-Rab7 switch (with SAND-1/CCZ-1 as its activator). The participation term early endosome to late endosome transport describes its role better than a positive regulation term. Proposed replacements: early endosome to late endosome transport Supporting Evidence: PMID:26783301 These data further suggest that SORF-1 and SORF-2 act in parallel with Rab switching genes (sand-1, ccz-1, rab-7, and tbc-2) to negatively regulate PtdIns3P on endosomes. PMID:17203072 SAND-1 is essential for RAB-7 function at the transition from early to late endosomes |
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Download this section (compressed HTML)Q: Which RAB-7 effectors in C. elegans (for example the HOPS complex, RILP-like adaptors, or HPO-27) are required for lysosome-phagosome fusion versus lysosome fission, and are they recruited by the same GTP-bound pool of RAB-7?
Q: Is the rab-7 requirement for RME-2 accumulation in oocytes a direct role in receptor recycling, or a secondary consequence of blocked early-to-late endosome conversion?
Q: The IGI rows from PMID:26783301 use GO:2000643 positive regulation of early endosome to late endosome transport for a Rab that is itself the core switch of that step. Should Rab-switch participants be annotated to GO:0045022 rather than to the regulation term?
Experiment: Compare GTP-locked (Q68L) and GDP-locked (T23N) RAB-7 in a rab-7(ok511) null background for rescue of lysosome-phagosome fusion and HPO-27 recruitment, combined with proximity labelling of RAB-7 on lysosomes to identify its effector set.
Hypothesis: GTP-bound RAB-7 recruits distinct effector sets for fusion and fission of lysosomes, and nucleotide cycling, not just GTP binding, is needed for phagolysosome formation.
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