BBS-8 is the C. elegans ortholog of human TTC8 (tetratricopeptide repeat protein 8), a core component of the BBSome complex. The BBSome is essential for intraflagellar transport (IFT) assembly and regulation. BBS-8 contains multiple TPR repeats that mediate protein-protein interactions within the complex. BBS-8 is required for proper BBSome assembly at the ciliary base, IFT particle integrity during transport, and IFT turnaround at the ciliary tip. Loss of BBS-8 results in dissociation of IFT-A and IFT-B subcomplexes during anterograde transport, leading to cilia structural defects and compromised sensory functions including chemotaxis, thermotaxis, and olfactory learning. BBS-8 localizes to the ciliary base, moves along the ciliary axoneme with IFT particles, and is enriched in ring-like structures at the base of specialized sensory compartments.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0034464 BBSome | IBA GO_REF:0000033 | ACCEPT | Summary: BBS-8 is a well-established core component of the BBSome complex. This annotation is supported by extensive phylogenetic evidence and direct experimental data showing that BBS-8 associates with other BBSome subunits (BBS-1, BBS-2, BBS-4, BBS-5, BBS-7, BBS-9) to form a functional complex (PMID:22922713). UniProt also confirms BBS-8 is "Part of BBSome complex, that contains at least bbs-1, bbs-2, bbs-4, bbs-5, osm-12, bbs-8/ttc-8 and bbs-9." Reason: Core function. BBSome membership is the most fundamental aspect of BBS-8 function. The BBSome controls IFT assembly and turnaround, and BBS-8 is essential for complex integrity. IBA annotation is strongly supported by experimental evidence from multiple C. elegans studies. Supporting Evidence: PMID:22922713 Further analyses revealed that the BBSome (refs 3, 4), a group of conserved proteins affected in human Bardet-Biedl syndrome(5) (BBS), assembles IFT complexes at the ciliary base file:worm/bbs-8/bbs-8-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0036064 ciliary basal body | IBA GO_REF:0000033 | ACCEPT | Summary: BBS-8 localizes predominantly at the ciliary basal body/base region, from which it facilitates IFT particle assembly. This is well-supported by multiple studies showing BBS-8 enrichment at the ciliary base in C. elegans (PMID:15231740, PMID:22922713, PMID:25335890). Reason: Core localization. The ciliary basal body is the primary site where BBS-8 performs its function in IFT assembly. Multiple experimental papers confirm this localization. Supporting Evidence: PMID:15231740 C. elegans BBS proteins localize predominantly at the base of cilia PMID:22922713 Further analyses revealed that the BBSome (refs 3, 4), a group of conserved proteins affected in human Bardet-Biedl syndrome(5) (BBS), assembles IFT complexes at the ciliary base |
| GO:0097730 non-motile cilium | IBA GO_REF:0000033 | ACCEPT | Summary: C. elegans sensory cilia are non-motile (primary) cilia, and BBS-8 localizes to these structures. This is directly demonstrated by localization studies in amphid and phasmid sensory neurons (PMID:15231740). Reason: Core localization. C. elegans sensory neurons contain non-motile cilia, and BBS-8 function is specific to these ciliated structures. Supporting Evidence: PMID:14520415 all available Caenorhabditis elegans BBS homologues are expressed exclusively in ciliated neurons PMID:15231740 C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme |
| GO:1905515 non-motile cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: BBS-8 is required for proper cilia assembly through its role in IFT regulation. Loss of BBS-8 results in structural defects in sensory cilia (PMID:15231740). Reason: Core function. BBS-8 regulates IFT assembly, which is essential for building and maintaining cilia. The term appropriately specifies non-motile cilia, which is accurate for C. elegans sensory cilia. Supporting Evidence: PMID:15231740 mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia PMID:22922713 Taken together, we conclude that the BBSome is required for assembling IFT particles at both ciliary base and tip |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: BBS-8 localizes to cilia in C. elegans sensory neurons. This is a broader term than the more specific IBA annotation to "non-motile cilium" but is nonetheless correct. Reason: Correct but general. This IEA annotation is subsumed by the more specific IBA annotation to non-motile cilium (GO:0097730), but retaining it does no harm. Supporting Evidence: PMID:15231740 C. elegans BBS proteins localize predominantly at the base of cilia |
| GO:0005930 axoneme | IEA GO_REF:0000044 | ACCEPT | Summary: BBS-8 undergoes bidirectional movement along the ciliary axoneme as part of IFT particles (PMID:15231740, PMID:22922713). It is transiently present on the axoneme during IFT transport. Reason: Correct localization. BBS-8 moves along the axoneme with IFT particles. While it is enriched at the ciliary base, it does transit through the axoneme during IFT cycles. Supporting Evidence: PMID:15231740 like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme PMID:22922713 Further analyses revealed that the BBSome (refs 3, 4), a group of conserved proteins affected in human Bardet-Biedl syndrome(5) (BBS), assembles IFT complexes at the ciliary base, then binds to the anterograde IFT particle in a DYF-2- (an orthologue of human WDR19) and BBS-1-dependent manner, and lastly reaches the ciliary tip to regulate proper IFT recycling |
| GO:0015031 protein transport | IEA GO_REF:0000043 | MODIFY | Summary: BBS-8 is involved in protein transport through its role in IFT regulation. The BBSome facilitates transport of membrane proteins and signaling molecules to cilia. However, this term is very general. Reason: Correct but overly general. BBS-8 specifically functions in ciliary protein transport via IFT. A more specific term would better capture the actual function. Proposed replacements: intraciliary transport Supporting Evidence: PMID:22922713 Further analyses revealed that the BBSome (refs 3, 4), a group of conserved proteins affected in human Bardet-Biedl syndrome(5) (BBS), assembles IFT complexes at the ciliary base, then binds to the anterograde IFT particle in a DYF-2- (an orthologue of human WDR19) and BBS-1-dependent manner, and lastly reaches the ciliary tip to regulate proper IFT recycling |
| GO:0030030 cell projection organization | IEA GO_REF:0000043 | MODIFY | Summary: This is a parent term of cilium organization. BBS-8 is involved in cilium assembly and maintenance, so this annotation is technically correct but very general. Reason: Overly general. The more specific term "cilium assembly" (GO:0060271) or "non-motile cilium assembly" (GO:1905515) would be more appropriate and is already annotated. Proposed replacements: cilium assembly Supporting Evidence: PMID:15231740 mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia |
| GO:0034464 BBSome | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate of the IBA annotation. InterPro domain IPR028796 (BBS8) correctly maps to BBSome membership. Reason: Correct. This IEA annotation is redundant with the IBA annotation but provides independent computational support for BBSome membership. Supporting Evidence: PMID:22922713 Further analyses revealed that the BBSome (refs 3, 4), a group of conserved proteins affected in human Bardet-Biedl syndrome(5) (BBS), assembles IFT complexes at the ciliary base |
| GO:1905515 non-motile cilium assembly | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate of the IBA annotation. InterPro mapping correctly identifies involvement in non-motile cilium assembly. Reason: Correct. Redundant with IBA annotation but provides additional computational support. Supporting Evidence: PMID:15231740 mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia |
| GO:0005929 cilium | NAS PMID:22922713 The BBSome controls IFT assembly and turnaround in cilia. | ACCEPT | Summary: This NAS annotation from ComplexPortal is based on the comprehensive study by Wei et al. demonstrating BBSome function in C. elegans cilia. Reason: Correct localization. The paper directly studies BBS protein localization and function in C. elegans cilia. Supporting Evidence: PMID:22922713 Further analyses revealed that the BBSome (refs 3, 4), a group of conserved proteins affected in human Bardet-Biedl syndrome(5) (BBS), assembles IFT complexes at the ciliary base, then binds to the anterograde IFT particle |
| GO:0060271 cilium assembly | NAS PMID:22922713 The BBSome controls IFT assembly and turnaround in cilia. | ACCEPT | Summary: This NAS annotation from ComplexPortal correctly captures that the BBSome (including BBS-8) is required for ciliogenesis. Reason: Core function. The BBSome is essential for IFT-dependent cilium assembly. Supporting Evidence: PMID:22922713 Taken together, we conclude that the BBSome is required for assembling IFT particles at both ciliary base and tip |
| GO:1903569 positive regulation of protein localization to ciliary membrane | IMP PMID:27930654 Whole-organism developmental expression profiling identifies... | ACCEPT | Summary: This annotation is based on the finding that BBS-8 is required for proper localization of RAB-28 to the periciliary membrane. In bbs-8 mutants, RAB-28(GTP) fails to localize properly to the periciliary membrane. Reason: Well-supported by experimental evidence. The BBSome/BBS-8 facilitates targeting of cargo proteins to ciliary membranes. Supporting Evidence: PMID:27930654 RAB-28 association with the periciliary membrane and IFT is dependent on GTP-binding and the BBSome subunit orthologue, BBS-8 |
| GO:1905798 positive regulation of intraciliary anterograde transport | IMP PMID:27930654 Whole-organism developmental expression profiling identifies... | ACCEPT | Summary: BBS-8 is required for proper anterograde IFT. In bbs-8 mutants, IFT-A and IFT-B dissociate during anterograde transport, indicating BBS-8 positively regulates the integrity of anterograde IFT particles. Reason: Core function. BBS-8/BBSome is essential for maintaining IFT particle integrity during anterograde transport. Loss of BBS-8 results in dissociation of IFT subcomplexes. Supporting Evidence: PMID:22922713 In bbs-7 and bbs-8 null worms, IFT-A and IFT-B dissociate in anterograde IFT transport, resulting in IFT-A moving alone with kinesin-II and IFT-B moving alone with OSM-3 |
| GO:1905801 positive regulation of intraciliary retrograde transport | IMP PMID:27930654 Whole-organism developmental expression profiling identifies... | ACCEPT | Summary: BBS-8 is required for proper retrograde IFT, particularly for the reassembly of IFT-B components into retrograde transport particles at the ciliary tip. Reason: Core function. The BBSome facilitates IFT turnaround at the ciliary tip, enabling proper retrograde transport. Loss of BBS-8 impairs IFT-B recycling. Supporting Evidence: PMID:22922713 Taken together, we conclude that the BBSome is required for assembling IFT particles at both ciliary base and tip PMID:22922713 The absence of the BBSome at the cilia tip leads to the defective recycling of IFT complex |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: This ND (No biological Data) annotation indicates no specific molecular function has been experimentally determined for BBS-8. While BBS-8 clearly has functions in IFT regulation, its direct molecular activity is not defined. Reason: Appropriate. BBS-8 functions primarily as a structural component of the BBSome complex. No specific enzymatic or binding activity has been characterized that would warrant a more specific MF term. The TPR repeats mediate protein-protein interactions within the complex, but this is captured by the CC annotation to BBSome. |
| GO:1904107 protein localization to microvillus membrane | IMP PMID:25335890 Ciliopathy proteins establish a bipartite signaling compartm... | MODIFY | Summary: This annotation is based on the finding that BBS-8 is required for proper localization of guanylyl cyclases in AFD neuron finger compartments, which contain microvilli-like structures. However, this annotation may be misleading as the structures in question are part of a specialized ciliary compartment rather than classical microvilli. Reason: The finger compartment of AFD neurons contains microvilli-like protrusions, but these are functionally a specialized ciliary signaling compartment. The term "protein localization to ciliary membrane" would be more accurate. The paper describes BBS-8 facilitating guanylyl cyclase localization to the base of the finger compartment, which is a cilium-related structure. Proposed replacements: protein localization to cilium Supporting Evidence: PMID:25335890 requires BBS-8 and DAF-25 (known as Ankmy2 in mammals) for correct localization of guanylyl cyclases needed for thermosensation |
| GO:0044292 dendrite terminus | IDA PMID:25335890 Ciliopathy proteins establish a bipartite signaling compartm... | ACCEPT | Summary: BBS-8 was observed at the dendrite terminus in AFD thermosensory neurons, specifically in ring-like structures between the base of the finger compartment and the dendritic membrane. Reason: Correct localization based on direct imaging. BBS-8 localizes to the dendrite terminus where the ciliary base/finger compartment interface is located. Supporting Evidence: PMID:25335890 One compartment, a bona fide cilium, is delineated by proteins associated with Bardet-Biedl syndrome (BBS), Meckel syndrome and nephronophthisis at its base |
| GO:0097546 ciliary base | IDA PMID:25335890 Ciliopathy proteins establish a bipartite signaling compartm... | ACCEPT | Summary: BBS-8 localizes to the ciliary base, the region where IFT particles are assembled before anterograde transport. This is a key site of BBS-8 function. Reason: Core localization. The ciliary base is the primary site of BBS-8 accumulation and function in IFT assembly. Supporting Evidence: PMID:15231740 C. elegans BBS proteins localize predominantly at the base of cilia |
| GO:0036064 ciliary basal body | IDA PMID:22922713 The BBSome controls IFT assembly and turnaround in cilia. | ACCEPT | Summary: Direct observation of BBS protein localization at the ciliary basal body in C. elegans. This is consistent with the IBA annotation. Reason: Core localization. Redundant with IBA annotation but provides direct experimental evidence. Supporting Evidence: PMID:22922713 Further analyses revealed that the BBSome (refs 3, 4), a group of conserved proteins affected in human Bardet-Biedl syndrome(5) (BBS), assembles IFT complexes at the ciliary base |
| GO:0097730 non-motile cilium | IDA PMID:15231740 Loss of C. elegans BBS-7 and BBS-8 protein function results ... | ACCEPT | Summary: Direct localization of BBS-8 to non-motile sensory cilia in C. elegans amphid and phasmid neurons. Reason: Core localization. Provides experimental support for the IBA annotation. Supporting Evidence: PMID:15231740 C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme |
| GO:0043005 neuron projection | IDA PMID:14520415 Basal body dysfunction is a likely cause of pleiotropic Bard... | ACCEPT | Summary: BBS-8 was observed in neuron projections in C. elegans. This is a general term that encompasses cilia and dendrites of sensory neurons. Reason: Correct but general. BBS-8 is expressed in ciliated sensory neurons and localizes to their projections (dendrites and cilia). Supporting Evidence: PMID:14520415 all available Caenorhabditis elegans BBS homologues are expressed exclusively in ciliated neurons |
| GO:1905515 non-motile cilium assembly | IEP PMID:14520415 Basal body dysfunction is a likely cause of pleiotropic Bard... | ACCEPT | Summary: Expression pattern evidence showing BBS-8 expression correlates with cilium assembly in ciliated neurons during development. Reason: Appropriate use of IEP. Expression during ciliogenesis supports involvement in cilium assembly, though this is weaker evidence than the IMP annotations. Supporting Evidence: PMID:14520415 BBS8 localizes specifically to ciliated structures PMID:14520415 contain regulatory elements for RFX, a transcription factor that modulates the expression of genes associated with ciliogenesis and intraflagellar transport |
| GO:0008355 olfactory learning | IMP PMID:17251413 Caenorhabditis elegans integrates the signals of butanone an... | KEEP AS NON CORE | Summary: bbs-8 mutants show defects in butanone enhancement, a form of olfactory learning. However, this is likely a secondary consequence of ciliary sensory defects rather than a direct function. Reason: This is a downstream phenotype rather than a direct function. BBS genes are required for AWC(ON) neuron function, and defects in this neuron lead to impaired olfactory learning. The primary function of BBS-8 is in cilium/IFT regulation, not learning per se. Supporting Evidence: PMID:17251413 Butanone enhancement also required the functions of Bardet-Biedl syndrome genes in the AWC(ON) neuron but not other genes that control ciliary transport |
| GO:0060271 cilium assembly | IMP PMID:15231740 Loss of C. elegans BBS-7 and BBS-8 protein function results ... | ACCEPT | Summary: bbs-8 mutants have defective cilia structure, demonstrating BBS-8 is required for normal cilium assembly. Reason: Core function. Direct mutant analysis shows BBS-8 is required for proper cilium formation. Supporting Evidence: PMID:15231740 mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia |
| GO:0006935 chemotaxis | IMP PMID:15231740 Loss of C. elegans BBS-7 and BBS-8 protein function results ... | KEEP AS NON CORE | Summary: bbs-8 mutants show defective chemotaxis behavior due to impaired sensory cilia function. Reason: This is a downstream phenotype resulting from ciliary sensory defects, not a direct molecular function of BBS-8. Chemotaxis defects are a consequence of impaired cilium function in sensory neurons. Supporting Evidence: PMID:15231740 some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction |
| GO:0042073 intraciliary transport | IMP PMID:15231740 Loss of C. elegans BBS-7 and BBS-8 protein function results ... | ACCEPT | Summary: BBS-8 is required for proper intraciliary transport (IFT). bbs-8 mutants show compromised IFT with IFT-A and IFT-B dissociation during transport. Reason: Core function. This is the primary molecular function of BBS-8 - regulating IFT particle assembly and transport. Direct evidence from multiple studies. Supporting Evidence: PMID:15231740 BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11 PMID:22922713 In bbs-7 and bbs-8 null worms, IFT-A and IFT-B dissociate in anterograde IFT transport, resulting in IFT-A moving alone with kinesin-II and IFT-B moving alone with OSM-3 |
| GO:0060090 molecular adaptor activity | ISS GO_REF:0000024 | NEW | Summary: BBS-8 functions as a structural adaptor within the BBSome complex, mediating protein-protein interactions through its TPR (tetratricopeptide repeat) domains. The BBSome acts as a cargo adaptor complex for IFT, and BBS-8 is essential for holding IFT-A and IFT-B subcomplexes together during transport (PMID:22922713). The TPR repeat architecture is a well-characterized protein-protein interaction scaffold. UniProt describes the BBSome as functioning as a "coat complex required for sorting of specific membrane proteins to the primary cilia." Reason: This molecular function annotation is proposed based on the structural role of BBS-8 within the BBSome. The protein contains 7-8 TPR repeats (UniProt), which are canonical protein-protein interaction domains. The BBSome functions as an adaptor/scaffold complex that organizes IFT particles and recruits cargo. BBS-8 is essential for maintaining IFT-A/IFT-B association. The ND annotation for molecular function should be replaced with this more informative term. Supporting Evidence: PMID:22922713 Combined with our findings that the BBSome controls IFT assembly at both ciliary base and tip, it is highly likely that the BBSome functions as a scaffold to organize IFT-A, IFT-B, ciliary membrane receptors, ciliary signaling molecules, and/or other IFT cargos into an entire unit and prepare it for IFT transport. PMID:22922713 The BBSome also shares the common structural features with COPI, COPII, and clathrin coats, and can directly recognize IFT cargos |
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Download this section (compressed HTML)Q: What is the precise molecular mechanism by which BBS-8 contributes to IFT-A/IFT-B complex stability during anterograde transport?
Q: Does BBS-8 have any direct cargo binding activity, or does it only function as a structural component of the BBSome?
Q: Are there specific TPR repeat domains in BBS-8 that mediate interactions with different BBSome subunits or IFT components?
Experiment: Structure-function analysis of BBS-8 TPR domains to identify specific regions required for BBSome assembly vs IFT association
Experiment: Crosslinking mass spectrometry to identify direct interaction partners of BBS-8 within the IFT machinery
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