OSM-3 is a homodimeric kinesin-2 family motor protein essential for intraflagellar transport (IFT) in C. elegans sensory cilia. It functions cooperatively with heterotrimeric kinesin-II to drive anterograde IFT in the middle segment of cilia, and is the sole motor for IFT in the distal segment where it builds the distal singlet microtubule region. OSM-3 is autoinhibited in a folded conformation and is activated upon binding to IFT particles. It is expressed exclusively in 26 chemosensory neurons (amphid, inner labial, and phasmid neurons). OSM-3 mutants have truncated cilia lacking distal segments and show defects in osmotic avoidance, chemotaxis, and dauer formation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-3 localizes to the cytoplasm including perinuclear regions and cell bodies of chemosensory neurons, where it exists in an autoinhibited compact conformation before being recruited to IFT particles (PMID:9950681, PMID:17000874). Reason: IBA annotation is phylogenetically well-supported. OSM-3 is present in the cytoplasm of neurons prior to ciliary entry, consistent with its autoinhibition mechanism. Supporting Evidence: PMID:9950681 a punctate localization pattern in the corresponding cell bodies and dendrites PMID:17000874 OSM-3 exists in the cytoplasm in a compact, autoinhibited state and that binding to an IFT particle relieves this autoinhibition file:worm/osm-3/osm-3-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0005871 kinesin complex | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-3 forms a homodimeric kinesin complex that functions as part of the IFT machinery in sensory cilia (PMID:9950681, PMID:17000874). Reason: OSM-3 is a dimeric kinesin motor. The IBA annotation is well-supported by phylogenetic evidence and confirmed by experimental data in C. elegans. Supporting Evidence: PMID:9950681 heterotrimeric CeKinesin-II and dimeric CeOsm-3 |
| GO:0005874 microtubule | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-3 is active along microtubules of the ciliary axoneme, moving processively along both doublet microtubules in the middle segment and singlet microtubules in the distal segment (PMID:17000874). Reason: Kinesin motors function on microtubules. OSM-3 translocates along axonemal microtubules during IFT. Supporting Evidence: PMID:17000874 OSM-3 was an active plus end-directed motor in a microtubule gliding assay |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-3 binds microtubules as part of its motor activity. The motor domain contains conserved microtubule-binding elements characteristic of kinesin motors (PMID:17000874). Reason: Microtubule binding is an essential property of kinesin motors. OSM-3 has a conserved kinesin motor domain with microtubule-binding capability. Supporting Evidence: PMID:17000874 OSM-3 was an active plus end-directed motor in a microtubule gliding assay |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-3 hydrolyzes ATP to power its motor activity. The wild-type protein has a basal ATPase rate of approximately 4 ATP/s/head that increases when autoinhibition is relieved (PMID:17000874). Reason: ATP hydrolysis is essential for kinesin motor function. Direct biochemical measurements confirm OSM-3 ATPase activity. Supporting Evidence: PMID:17000874 low microtubule-stimulated adenosine triphosphatase (ATPase) activity |
| GO:0043005 neuron projection | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-3 is localized to chemosensory neuron projections including dendrites and their ciliated endings (PMID:9950681). Reason: OSM-3 localizes along the dendrites of chemosensory neurons extending to the ciliated endings. Supporting Evidence: PMID:9950681 a punctate localization pattern in the corresponding cell bodies and dendrites |
| GO:0005929 cilium | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-3 localizes to sensory cilia where it functions in IFT. It localizes along the full cilium length including both middle and distal segments (PMID:9950681). Reason: Core cellular localization for OSM-3 function. IBA is well-supported and confirmed by multiple IDA annotations. Supporting Evidence: PMID:9950681 an intense concentration of CeKinesin-II and CeOsm-3 polypeptides in the ciliated endings of these chemosensory neurons |
| GO:0030030 cell projection organization | IBA GO_REF:0000033 | MODIFY | Summary: OSM-3 is required for organizing the distal segment of sensory cilia. Loss of OSM-3 results in cilia lacking distal segments (PMID:17000874). Reason: While technically accurate, this term is too general. OSM-3 has a specific role in cilium organization, not cell projections broadly. Proposed replacements: cilium assembly non-motile cilium assembly |
| GO:0005815 microtubule organizing center | IBA GO_REF:0000033 | MODIFY | Summary: OSM-3 localizes to the ciliary basal body, which serves as the MTOC for the cilium (PMID:27623382). Reason: While basal bodies are MTOCs, the more precise term for OSM-3 localization is ciliary basal body, which is experimentally validated. Proposed replacements: ciliary basal body |
| GO:0098971 anterograde dendritic transport of neurotransmitter receptor complex | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: This annotation is based on the mammalian homolog KIF17, which transports neurotransmitter receptors in dendrites. However, OSM-3 in C. elegans functions primarily in ciliary IFT rather than dendritic receptor transport. Reason: This function is established for mammalian KIF17 but not demonstrated for C. elegans OSM-3. OSM-3 is specifically involved in ciliary transport, not general dendritic transport of receptor complexes. Supporting Evidence: PMID:17000874 Autoinhibition regulates the motility of the C. |
| GO:0008574 plus-end-directed microtubule motor activity | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-3 is a plus-end directed motor that drives anterograde transport in cilia. This is confirmed by direct in vitro assays (PMID:17000874). Reason: Core molecular function of OSM-3. IBA is well-supported and confirmed by IDA. Supporting Evidence: PMID:17000874 OSM-3 was an active plus end-directed motor in a microtubule gliding assay |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: OSM-3 binds nucleotides (ATP/ADP) as part of its motor cycle. UniProt annotates ATP binding based on keywords. Reason: Correct but less informative than ATP binding. The IEA is acceptable as a broader parent annotation. |
| GO:0003777 microtubule motor activity | IEA GO_REF:0000120 | ACCEPT | Summary: OSM-3 is a microtubule motor that moves along microtubules. This is the general molecular function for kinesin motors. Reason: Core molecular function. IEA is appropriate as this is confirmed by experimental data. Supporting Evidence: PMID:17000874 OSM-3 was an active plus end-directed motor in a microtubule gliding assay |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: OSM-3 binds ATP at its motor domain for hydrolysis. The UniProt entry notes the ATP binding site at residues 87-94. Reason: Essential molecular function for kinesin motors. Strongly supported by domain analysis and biochemical data. Supporting Evidence: PMID:17000874 microtubule-stimulated adenosine triphosphatase (ATPase) activity |
| GO:0005856 cytoskeleton | IEA GO_REF:0000120 | ACCEPT | Summary: OSM-3 localizes to the cytoskeleton, specifically the microtubule-based axoneme of cilia. Reason: General localization term that is accurate for a microtubule motor. |
| GO:0005874 microtubule | IEA GO_REF:0000043 | ACCEPT | Summary: Duplicate of IBA annotation. OSM-3 is active on microtubules. Reason: Correct annotation, duplicates IBA with different evidence code. |
| GO:0005929 cilium | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of IBA annotation. OSM-3 localizes to sensory cilia. Reason: Correct annotation, duplicates IBA with different evidence code. |
| GO:0005930 axoneme | IEA GO_REF:0000044 | ACCEPT | Summary: OSM-3 localizes to and functions along the ciliary axoneme, transporting IFT particles (PMID:17000874). Reason: Correct and specific localization for OSM-3 within the cilium. |
| GO:0007018 microtubule-based movement | IEA GO_REF:0000120 | MODIFY | Summary: OSM-3 drives microtubule-based movement of IFT particles within cilia. Reason: While accurate, a more specific term exists for OSM-3's biological process. Proposed replacements: intraciliary anterograde transport |
| GO:0008017 microtubule binding | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate of IBA annotation. OSM-3 binds microtubules via its motor domain. Reason: Correct annotation, duplicates IBA with different evidence code (InterPro). |
| GO:0032839 dendrite cytoplasm | IEA GO_REF:0000108 | ACCEPT | Summary: This annotation is inferred from the dendritic transport annotation. OSM-3 does localize to dendrites of sensory neurons (PMID:9950681). Reason: OSM-3 is present in dendrite cytoplasm en route to cilia. Supporting Evidence: PMID:9950681 a punctate localization pattern in the corresponding cell bodies and dendrites |
| GO:0032991 protein-containing complex | IEA GO_REF:0000117 | MODIFY | Summary: OSM-3 forms homodimeric complexes and associates with IFT particles. Reason: Too general. OSM-3 specifically forms kinesin complexes. Proposed replacements: kinesin complex |
| GO:0030425 dendrite | IDA PMID:9950681 Two heteromeric kinesin complexes in chemosensory neurons an... | ACCEPT | Summary: OSM-3::GFP localizes to dendrites of chemosensory neurons as shown by immunolocalization (PMID:9950681). Reason: Direct experimental evidence from immunolocalization studies. Supporting Evidence: PMID:9950681 a punctate localization pattern in the corresponding cell bodies and dendrites |
| GO:1902856 negative regulation of non-motile cilium assembly | IGI PMID:17420466 Mutation of the MAP kinase DYF-5 affects docking and undocki... | UNDECIDED | Summary: In dyf-5 mutants, OSM-3 accumulates and moves at reduced speed, and cilia become elongated. This suggests complex regulatory interactions affecting cilium length (PMID:17420466). Reason: The relationship between OSM-3 and negative regulation of cilium assembly is indirect and context-dependent (dyf-5 mutant background). OSM-3 primarily promotes cilium assembly; negative regulation may be a secondary effect. Supporting Evidence: PMID:17420466 Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans. |
| GO:1902857 positive regulation of non-motile cilium assembly | IGI PMID:17420466 Mutation of the MAP kinase DYF-5 affects docking and undocki... | ACCEPT | Summary: OSM-3 is required for assembly of the distal segment of sensory cilia. Loss of OSM-3 results in truncated cilia (PMID:17420466, PMID:17000874). Reason: OSM-3 is essential for building distal segments and thus positively regulates cilium assembly. Supporting Evidence: PMID:17420466 OSM-3 alone mediates transport in the distal segments PMID:17000874 osm-3-null animals only display a loss of the distal segments of their sensory cilia |
| GO:0035720 intraciliary anterograde transport | IMP PMID:17420466 Mutation of the MAP kinase DYF-5 affects docking and undocki... | ACCEPT | Summary: OSM-3 drives anterograde IFT in cilia. Mutations affect IFT velocity and docking/undocking of kinesin motors (PMID:17420466). Reason: Core biological function of OSM-3. IMP evidence from dyf-5 mutant studies. Supporting Evidence: PMID:17420466 anterograde intraflagellar transport (IFT) is mediated by two kinesin-2 complexes, kinesin II and OSM-3 kinesin |
| GO:0035720 intraciliary anterograde transport | IGI PMID:17420466 Mutation of the MAP kinase DYF-5 affects docking and undocki... | ACCEPT | Summary: Genetic interaction with dyf-5 demonstrates OSM-3's role in anterograde IFT. Reason: Supports the IMP annotation with genetic interaction evidence. Supporting Evidence: PMID:17420466 OSM-3 moves at a reduced speed and is not attached to IFT particles |
| GO:0036064 ciliary basal body | IDA PMID:27623382 A Conserved Role for Girdin in Basal Body Positioning and Ci... | ACCEPT | Summary: OSM-3 localizes to the ciliary basal body as shown by fluorescence microscopy studies examining basal body positioning (PMID:27623382). Reason: Direct experimental localization data from the Girdin study. Supporting Evidence: PMID:27623382 A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis. |
| GO:0042073 intraciliary transport | IDA PMID:27623382 A Conserved Role for Girdin in Basal Body Positioning and Ci... | ACCEPT | Summary: OSM-3 functions in intraciliary transport as demonstrated by its localization and movement along the ciliary axoneme. Reason: Core biological function of OSM-3. Supporting Evidence: PMID:27623382 A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis. |
| GO:0097730 non-motile cilium | IDA PMID:17420466 Mutation of the MAP kinase DYF-5 affects docking and undocki... | ACCEPT | Summary: OSM-3 localizes to non-motile sensory cilia in C. elegans chemosensory neurons (PMID:17420466). Reason: C. elegans sensory cilia are non-motile (primary) cilia. OSM-3 localizes to these structures. Supporting Evidence: PMID:17420466 In the cilia of the nematode Caenorhabditis elegans |
| GO:1902857 positive regulation of non-motile cilium assembly | IMP PMID:17420466 Mutation of the MAP kinase DYF-5 affects docking and undocki... | ACCEPT | Summary: osm-3 mutants lack distal cilium segments, demonstrating OSM-3's role in promoting cilium assembly (PMID:17420466). Reason: Mutant phenotype analysis supports positive regulation of cilium assembly. Supporting Evidence: PMID:17420466 OSM-3 alone mediates transport in the distal segments |
| GO:0035720 intraciliary anterograde transport | IDA PMID:17000874 Autoinhibition regulates the motility of the C. elegans intr... | ACCEPT | Summary: Single-molecule analysis demonstrates OSM-3 is a processive motor capable of anterograde transport when autoinhibition is relieved (PMID:17000874). Reason: Direct in vitro demonstration of OSM-3 motor activity consistent with anterograde IFT function. Supporting Evidence: PMID:17000874 OSM-3 is a Kinesin-2 family member from Caenorhabditis elegans that is involved in intraflagellar transport (IFT), a process essential for the construction and maintenance of sensory cilia |
| GO:0035720 intraciliary anterograde transport | IDA PMID:17000880 Mechanism of transport of IFT particles in C. elegans cilia ... | ACCEPT | Summary: Live imaging shows OSM-3 and kinesin-II cooperatively drive anterograde IFT in the middle segment, while OSM-3 alone transports in the distal segment (PMID:17000880). Reason: Definitive demonstration of OSM-3's role in anterograde IFT through live imaging studies. Supporting Evidence: PMID:17000874 Microscopy studies in living C. elegans have shown that both motors cooperate to move IFT particles along the middle segment of the cilia PMID:17000880 Mechanism of transport of IFT particles in C. |
| GO:0035720 intraciliary anterograde transport | IMP PMID:26863025 A Screen for Modifiers of Cilia Phenotypes Reveals Novel MKS... | ACCEPT | Summary: osm-3 mutations affect IFT velocity in cilia, with the yhw66 allele reducing anterograde IFT rates (PMID:26863025). Reason: Mutant phenotype analysis confirms OSM-3's role in anterograde IFT. Supporting Evidence: PMID:26863025 In osm-3(yhw66) mutants anterograde intraflagellar transport (IFT) velocity is reduced |
| GO:1905515 non-motile cilium assembly | IGI PMID:26863025 A Screen for Modifiers of Cilia Phenotypes Reveals Novel MKS... | ACCEPT | Summary: Genetic interactions between osm-3 and nphp-4 affect distal segment formation of non-motile cilia (PMID:26863025). Reason: Genetic interaction data supports OSM-3's role in cilium assembly. Supporting Evidence: PMID:26863025 nphp-4(tm925);osm-3(yhw66) double mutants lack distal segments and are dye-filling (Dyf) and osmotic avoidance (Osm) defective, similar to osm-3(mn357) null mutants |
| GO:0061066 positive regulation of dauer larval development | IMP PMID:7828815 Multiple chemosensory defects in daf-11 and daf-21 mutants o... | KEEP AS NON CORE | Summary: osm-3 mutations affect chemosensory function and dauer formation. The annotation suggests OSM-3 promotes dauer development (PMID:7828815). Reason: Dauer phenotype is secondary to ciliary defects. OSM-3 mutants have defective sensory cilia which impairs pheromone sensing required for dauer decision. This is not a core function but a downstream consequence. Supporting Evidence: PMID:7828815 Multiple chemosensory defects in daf-11 and daf-21 mutants of Caenorhabditis elegans. |
| GO:0043053 dauer entry | IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | KEEP AS NON CORE | Summary: Genetic analysis shows osm-3 affects dauer entry through chemosensory defects (PMID:1732156). Reason: Dauer phenotype is secondary to ciliary defects. OSM-3's role in dauer is indirect through its effects on sensory cilia function. Supporting Evidence: PMID:1732156 Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia, thereby blocking chemosensation |
| GO:0060271 cilium assembly | IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | ACCEPT | Summary: Genetic analysis places osm-3 among genes required for proper cilium structure (PMID:1732156). Reason: Core biological function of OSM-3 - required for distal segment assembly. Supporting Evidence: PMID:1732156 Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia |
| GO:0097730 non-motile cilium | IDA PMID:22342749 Endocytosis genes facilitate protein and membrane transport ... | ACCEPT | Summary: OSM-3 localization in sensory cilia shown by fluorescence microscopy in endocytosis study (PMID:22342749). Reason: Direct localization data supporting ciliary localization. Supporting Evidence: PMID:22342749 Feb 16. Endocytosis genes facilitate protein and membrane transport in C. |
| GO:0036064 ciliary basal body | IDA PMID:22922713 The BBSome controls IFT assembly and turnaround in cilia. | ACCEPT | Summary: OSM-3 localizes to the basal body region in the context of BBSome-IFT assembly studies (PMID:22922713). Reason: Direct experimental evidence from comprehensive IFT study. Supporting Evidence: PMID:22922713 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:0097730 non-motile cilium | IDA PMID:9950681 Two heteromeric kinesin complexes in chemosensory neurons an... | ACCEPT | Summary: First demonstration of OSM-3 localization in sensory cilia using GFP reporters and immunolocalization (PMID:9950681). Reason: Seminal paper establishing OSM-3 ciliary localization. Supporting Evidence: PMID:9950681 an intense concentration of CeKinesin-II and CeOsm-3 polypeptides in the ciliated endings of these chemosensory neurons |
| GO:0008574 plus-end-directed microtubule motor activity | IDA PMID:17000874 Autoinhibition regulates the motility of the C. elegans intr... | ACCEPT | Summary: Single-molecule assays directly demonstrate OSM-3 is a plus-end directed motor (PMID:17000874). Reason: Core molecular function with direct biochemical evidence. Supporting Evidence: PMID:17000874 OSM-3 was an active plus end-directed motor in a microtubule gliding assay |
| GO:0003777 microtubule motor activity | IDA PMID:17000880 Mechanism of transport of IFT particles in C. elegans cilia ... | ACCEPT | Summary: Live imaging demonstrates OSM-3 motor activity in IFT transport at measured velocities (PMID:17000880). Reason: Core molecular function with direct in vivo evidence. Supporting Evidence: PMID:17000880 The assembly and function of cilia on Caenorhabditis elegans neurons depends on the action of two kinesin-2 motors, heterotrimeric kinesin-II and homodimeric OSM-3-kinesin, which cooperate to move the same intraflagellar transport (IFT) particles along microtubule (MT) doublets |
| GO:0005871 kinesin complex | IDA PMID:17000880 Mechanism of transport of IFT particles in C. elegans cilia ... | ACCEPT | Summary: OSM-3 forms homodimeric kinesin complexes as demonstrated by biochemical and imaging studies (PMID:17000880). Reason: Direct experimental evidence for kinesin complex formation. Supporting Evidence: PMID:17000880 heterotrimeric kinesin-II and homodimeric OSM-3-kinesin, which cooperate to move the same intraflagellar transport (IFT) particles along microtubule (MT) doublets |
| GO:0043025 neuronal cell body | IDA PMID:9950681 Two heteromeric kinesin complexes in chemosensory neurons an... | ACCEPT | Summary: OSM-3 localizes to the cell bodies of chemosensory neurons as shown by immunolocalization and GFP reporters (PMID:9950681). Reason: Direct localization data in neuronal cell bodies. Supporting Evidence: PMID:9950681 a punctate localization pattern in the corresponding cell bodies |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:9950681 Two heteromeric kinesin complexes in chemosensory neurons an... | ACCEPT | Summary: OSM-3 shows punctate localization in the perinuclear region of chemosensory neuron cell bodies (PMID:9950681). Reason: Detailed localization consistent with autoinhibited motor waiting to be recruited to IFT. Supporting Evidence: PMID:9950681 a punctate localization pattern in the corresponding cell bodies |
| GO:0046626 regulation of insulin receptor signaling pathway | IGI PMID:11381260 Regulation of the Caenorhabditis elegans longevity protein D... | MARK AS OVER ANNOTATED | Summary: This annotation is based on genetic interactions affecting DAF-16 regulation and lifespan. The study shows sensory neurons affect DAF-16 localization and aging, but OSM-3's role is indirect through ciliary function (PMID:11381260). Reason: The connection to insulin signaling is indirect. OSM-3 mutations cause ciliary defects that affect sensory neuron function. Sensory neurons in turn regulate insulin signaling. OSM-3 does not directly regulate insulin receptor signaling; it enables proper ciliary function in sensory neurons. Supporting Evidence: PMID:11381260 Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. |
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Download this section (compressed HTML)Q: What is the structural basis for OSM-3 autoinhibition and how does cargo binding relieve it? The G444E mutation in the hinge region activates OSM-3, suggesting specific conformational regulation that could be elucidated structurally.
Q: How is OSM-3 specifically recruited to IFT particles and what role does phosphorylation at S316 play? The S316F mutation has NPHP-4 dependent effects, suggesting complex regulation of OSM-3 recruitment to IFT machinery.
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