OSM-6 is the Caenorhabditis elegans ortholog of human IFT52 (also called NGD5; Chlamydomonas IFT52/BLD1) and is a core structural subunit of the intraflagellar transport complex B (IFT-B). Intraflagellar transport is the bidirectional, microtubule-motor-driven movement of large multiprotein particles that build and maintain cilia: kinesin-2 motors carry IFT particles and their cargo anterogradely from the ciliary base to the tip, and cytoplasmic dynein-2 returns them retrogradely. OSM-6/IFT52 is itself a component (and moving cargo) of the IFT-B particle rather than an enzyme; its GATase-like N-terminal (GIFT) domain, central domain and C-terminal domain are used to scaffold the complex. In C. elegans, osm-6 is expressed exclusively in ciliated sensory neurons under control of the RFX transcription factor DAF-19, and the protein localizes to the ciliary base (basal body, transition zone), along the sensory (non-motile) cilium, and in the cytoplasm/cell body of these neurons. OSM-6 is required for assembly of the ciliary axoneme: loss-of-function mutants retain normal transition zones but have severely truncated axonemes and ectopic microtubule assembly, causing dye-filling defects. Because the 60 ciliated sensory neurons mediate chemosensation, osmotic avoidance, mechanosensation, and dauer-pathway signaling, osm-6 mutants are broadly defective in these sensory behaviors as a downstream consequence of lacking functional cilia. OSM-6/IFT52 is conserved from algae to humans, and the pathway it serves is central to the biology of ciliopathies.
Definition: A structural molecule activity in which a protein acts as a structural subunit of an intraflagellar transport (IFT) particle (IFT-A or IFT-B), contributing to the assembly and integrity of the particle that is trafficked along the ciliary axoneme by kinesin-2 and dynein-2 motors.
Justification: OSM-6/IFT52 and its IFT-B/IFT-A paralogs act as structural subunits of the IFT particle, a role currently expressible only as the generic GO:0005198 structural molecule activity. A dedicated MF term would capture the shared function of IFT structural subunits.
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005929 cilium | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-6/IFT52 localizes to and functions within the cilium; phylogenetic (IBA) inference agrees with direct C. elegans localization data. Reason: Cilium localization is directly supported by multiple experimental studies (OSM-6::GFP is a canonical ciliary/IFT marker) and is a core aspect of osm-6 function. Supporting Evidence: PMID:22922713 the GFP-tagged IFT-B component OSM-6 (the ortholog of human IFT52) |
| GO:0030992 intraciliary transport particle B | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-6 is a structural subunit of the IFT-B particle; this is the single most important annotation for the gene and is supported by orthology to IFT52 and by ComplexPortal (CPX-1290). Reason: Core molecular role. OSM-6 is explicitly the IFT-B component / IFT52 ortholog and a member of Intraflagellar transport complex B (CPX-1290). Supporting Evidence: PMID:22922713 the GFP-tagged IFT-B component OSM-6 (the ortholog of human IFT52) |
| GO:0042073 intraciliary transport | IBA GO_REF:0000033 | ACCEPT | Summary: As an IFT-B subunit and moving IFT cargo, OSM-6 is directly involved in intraciliary transport. Reason: Core biological process. OSM-6::GFP moves bidirectionally by IFT and is part of the transported IFT particle. Supporting Evidence: PMID:10545497 OSM-1 and OSM-6, all move at approximately 1.1 microm/s in the retrograde direction along cilia and dendrites |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: OSM-6 is required for building the ciliary axoneme; phylogenetic inference is corroborated by the loss-of-function ultrastructural phenotype. Reason: Core process. osm-6 mutants have severely truncated axonemes, establishing a role in cilium assembly. Supporting Evidence: PMID:2428682 The cilia in che-13 (e1805), osm-1 (p808), osm-5 (p813), and osm-6 (p811) mutants have normal transition zones and severely shortened axonemes. |
| GO:0005814 centriole | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically propagated centriole localization. In C. elegans the directly demonstrated basal-body/transition-zone localization is the relevant structure (the ciliary basal body is a docked, modified centriole). Reason: Plausible but not the core functional site and not directly demonstrated in C. elegans; the experimentally supported location is the ciliary basal body (GO:0036064). Retained as a non-core, orthology-based location rather than removed. |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal (CPX-1290) statement that OSM-6 localizes to the cilium, consistent with direct experimental data. Reason: Core ciliary localization; corroborated by IDA evidence from multiple studies. Supporting Evidence: PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphasic in C. elegans Sensory Cilia |
| GO:0030992 intraciliary transport particle B | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal assertion of OSM-6 membership in IFT particle B, the core structural annotation, based on the C. elegans IFT-B complex. Reason: Core molecular role, redundant with and reinforcing the IBA IFT-B membership annotation. Supporting Evidence: PMID:28479320 Disruption of the dynein-2 tail domain, light intermediate chain, or intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary localization |
| GO:0042073 intraciliary transport | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal statement of IFT-B involvement in intraciliary transport. Reason: Core process consistent with OSM-6 being a transported IFT-B subunit. Supporting Evidence: PMID:28479320 Disruption of the dynein-2 tail domain, light intermediate chain, or intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary localization |
| GO:0060271 cilium assembly | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal statement of IFT-B involvement in cilium assembly. Reason: Core process; redundant with the IMP/IBA cilium-assembly annotations. Supporting Evidence: PMID:2428682 The cilia in che-13 (e1805), osm-1 (p808), osm-5 (p813), and osm-6 (p811) mutants have normal transition zones and severely shortened axonemes. |
| GO:0060271 cilium assembly | IMP PMID:24013594 Neuropeptide signaling remodels chemosensory circuit composi... | ACCEPT | Summary: osm-6 loss abolishes functional sensory cilia (dendritic endings), confirming a requirement in cilium assembly. Reason: Core process. Although this paper is about a salt circuit, it explicitly uses osm-6 as a cilium-assembly loss-of-function allele. Supporting Evidence: PMID:24013594 We analyzed hypomorphic osm-6 mutants that lack functional sensory cilia (dendritic endings) |
| GO:1902075 cellular response to salt | IMP PMID:24013594 Neuropeptide signaling remodels chemosensory circuit composi... | KEEP AS NON CORE | Summary: osm-6 mutants have reduced salt-evoked neuronal responses, but only because they lack functional cilia; OSM-6 has no salt-sensing or salt-signalling activity of its own. Reason: Indirect, downstream sensory phenotype of ciliary loss rather than a core molecular/biological function of OSM-6. Retained (per curator) but marked non-core to avoid implying a direct salt-response role. Supporting Evidence: PMID:24013594 found them to have greatly reduced ASEL salt responses and AWCON salt and odor responses |
| GO:0005929 cilium | IDA PMID:27930654 Whole-Organism Developmental Expression Profiling Identifies... | ACCEPT | Summary: Direct localization of OSM-6::GFP to the cilium, used as a ciliary reference marker. Reason: Core ciliary localization directly observed; OSM-6::GFP (IFT52 orthologue) is imaged throughout normal-length cilia. Supporting Evidence: PMID:27930654 Localisation of an IFT protein, OSM-6 (IFT52 orthologue), throughout normal-length cilia confirms this finding |
| GO:1905515 non-motile cilium assembly | IMP PMID:2428682 Mutant sensory cilia in the nematode Caenorhabditis elegans. | ACCEPT | Summary: osm-6 mutants fail to build full sensory (non-motile) cilia; this is the most precise cilium-assembly term for the worm's sensory cilia. Reason: Core process, and appropriately specific (C. elegans sensory cilia are non-motile). Directly supported by the ultrastructural phenotype. Supporting Evidence: PMID:2428682 The cilia in che-13 (e1805), osm-1 (p808), osm-5 (p813), and osm-6 (p811) mutants have normal transition zones and severely shortened axonemes. |
| GO:0060271 cilium assembly | IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | ACCEPT | Summary: Genetic-interaction evidence placing osm-6 among cilium-structure genes required for chemosensory cilium function in the dauer pathway. Reason: Core process; osm-6 is one of nine genes whose mutation gives structurally defective chemosensory cilia. Supporting Evidence: PMID:1732156 Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia, thereby blocking chemosensation. |
| GO:0097730 non-motile cilium | IDA PMID:22342749 Endocytosis genes facilitate protein and membrane transport ... | ACCEPT | Summary: Direct localization of OSM-6 to the sensory (non-motile) cilium. Reason: Core ciliary localization; the sensory-cilium term is appropriately specific. Supporting Evidence: PMID:22342749 cilium-based intraflagellar transport (IFT) |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root-level placeholder recording that no specific molecular function had been assigned at the time of annotation. Reason: Retained as the standard ND placeholder. A subunit-specific molecular function (structural molecule activity within IFT-B) is now proposed as a NEW annotation and in core_functions; no catalytic activity is known or expected for this GATase-fold scaffold. |
| GO:0005198 structural molecule activity | IBA GO_REF:0000033 | NEW | Summary: OSM-6/IFT52 has no catalytic activity; as an IFT-B subunit its molecular function is best captured as a subunit-specific structural molecule activity. Reason: Proposed new molecular-function annotation reflecting OSM-6's role as a structural subunit of the IFT-B particle (the current GOA carries only the ND root MF for this gene). This IBA/GO_REF:0000033 evidence pairing does NOT currently exist in the GOA export; it is the expected phylogenetic evidence basis if the annotation were made (IFT52 orthologues across species are IFT-B structural subunits). Ideally a more specific 'structural constituent of intraflagellar transport particle' term (see proposed_new_terms) would be used. Supporting Evidence: PMID:22922713 the GFP-tagged IFT-B component OSM-6 (the ortholog of human IFT52) |
| GO:0036064 ciliary basal body | IDA PMID:22922713 The BBSome controls IFT assembly and turnaround in cilia. | ACCEPT | Summary: OSM-6::GFP directly localizes to the ciliary basal body, where IFT particles assemble before entering the cilium. Reason: Core localization at the site of IFT assembly. Supporting Evidence: PMID:22922713 the GFP-tagged IFT-B component OSM-6 (the ortholog of human IFT52) |
| GO:0035869 ciliary transition zone | IDA PMID:10545497 Role of a class DHC1b dynein in retrograde transport of IFT ... | ACCEPT | Summary: OSM-6::GFP is observed at/through the ciliary transition zone as it moves between the base and the axoneme. Reason: Core localization consistent with IFT trafficking through the transition zone. Supporting Evidence: PMID:10545497 OSM-1 and OSM-6, all move at approximately 1.1 microm/s in the retrograde direction along cilia and dendrites |
| GO:0097730 non-motile cilium | IDA PMID:10545497 Role of a class DHC1b dynein in retrograde transport of IFT ... | ACCEPT | Summary: OSM-6::GFP localizes along the sensory (non-motile) cilium. Reason: Core ciliary localization, appropriately specific. Supporting Evidence: PMID:10545497 OSM-1 and OSM-6, all move at approximately 1.1 microm/s in the retrograde direction along cilia and dendrites |
| GO:0005737 cytoplasm | IDA PMID:9475731 Analysis of osm-6, a gene that affects sensory cilium struct... | KEEP AS NON CORE | Summary: OSM-6::GFP is present in the cytoplasm (including neuronal processes) prior to and outside of ciliary transport. Reason: Directly observed but a broad, non-informative location; the functionally relevant sites are the cilium and its base. Retained as non-core. Supporting Evidence: PMID:9475731 The OSM-6::GFP protein was localized to cytoplasm, including processes and dendritic endings where sensory cilia are situated. |
| GO:0006935 chemotaxis | IMP PMID:2428682 Mutant sensory cilia in the nematode Caenorhabditis elegans. | KEEP AS NON CORE | Summary: osm-6 mutants are chemosensory-defective (dye-filling defective) because their chemosensory cilia are truncated. Reason: Downstream sensory consequence of defective cilia rather than a direct role of OSM-6 in chemotaxis signalling. Retained but non-core. Supporting Evidence: PMID:2428682 Mutations in 14 genes prevent dye uptake and disrupt chemosensory behaviors. |
| GO:0006970 response to osmotic stress | IMP PMID:730048 Osmotic avoidance defective mutants of the nematode Caenorha... | KEEP AS NON CORE | Summary: osm-6 is named for its osmotic-avoidance-defective phenotype; mutants fail to avoid high osmolarity because their sensory cilia are non-functional. Reason: Indirect, downstream behavioral phenotype of ciliary loss, not a direct osmotic-stress-response activity of OSM-6. Retained (curator IMP) but non-core. Supporting Evidence: PMID:730048 mutants were selected for their inability to avoid high concentrations of fructose or NaCl |
| GO:0043025 neuronal cell body | IDA PMID:9475731 Analysis of osm-6, a gene that affects sensory cilium struct... | KEEP AS NON CORE | Summary: OSM-6::GFP accumulates in the cell bodies of ciliated sensory neurons, where the protein is synthesized before delivery to cilia. Reason: Real localization but reflects the site of synthesis rather than the core functional site (the cilium/basal body). Retained as non-core. Supporting Evidence: PMID:9475731 showed accumulation of GFP in ciliated sensory neurons exclusively |
| GO:0050954 sensory perception of mechanical stimulus | IMP PMID:8460126 A dual mechanosensory and chemosensory neuron in Caenorhabdi... | KEEP AS NON CORE | Summary: Nose-touch mechanosensation requires intact ciliated sensory endings, which osm-6 is needed to build; osm-6 mutants are mechanosensory-defective. Reason: Downstream sensory consequence of defective cilia rather than a direct mechanotransduction role of OSM-6. The cached abstract does not name osm-6, but the WormBase IMP reflects curator full-text evidence and is not overruled. Supporting Evidence: PMID:8460126 Mutant animals that have defective ciliated sensory endings as well as laser-operated animals that lack ASH, FLP, and OLQ fail to respond to touch to the nose. |
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Download this section (compressed HTML)Q: Which IFT-B subunits does OSM-6 directly contact in C. elegans, and are the GIFT, central and C-terminal domains functionally separable?
Suggested experts: Oliver E. Blacque
Q: Does the IFT52 GIFT domain retain any ligand-binding capacity, or is it a purely structural remnant of the glutamine-amidotransferase fold?
Experiment: Perform in vivo proximity labeling (TurboID) with domain-truncated OSM-6 variants expressed in ciliated neurons, followed by mass spectrometry, to map domain-specific IFT-B interaction partners.
Hypothesis: OSM-6/IFT52 bridges the IFT-B core to peripheral subunits via distinct domains, and disrupting individual domains selectively destabilizes parts of IFT-B.
Type: proximity labeling / interaction mapping
Experiment: Use live imaging of tagged tubulin and IFT trains in osm-6 partial loss-of-function backgrounds to quantify anterograde cargo delivery versus transition-zone integrity.
Hypothesis: The severely truncated axoneme of osm-6 mutants reflects failure to deliver axonemal tubulin/cargo by IFT-B rather than a transition-zone defect.
Type: live-cell imaging
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The specific intra-complex protein contacts of OSM-6/IFT52 within the C. elegans IFT-B particle have not been experimentally mapped. In other organisms IFT52 bridges the IFT-B1 core (contacting IFT88, IFT70 and IFT46) and links the core to peripheral subunits, but which partners its GIFT, central and C-terminal domains engage in the worm, and how these contacts are used during IFT-particle assembly and tip turnaround, is undetermined.
OPEN BIOLOGYONTOLOGY MF_DARK
What is known: It is firmly established that OSM-6 is an IFT-B/IFT52 structural subunit that moves bidirectionally by IFT, localizes to basal body, transition zone and axoneme, and is required for axoneme assembly.
Significance: Defining OSM-6's specific IFT-B contacts would explain how the IFT-B particle is built and how ciliopathy-relevant IFT52 mutations destabilize the complex.
What would resolve it: In vivo proximity labeling (BioID/TurboID) or cross-linking mass spectrometry of tagged OSM-6 in ciliated neurons, plus structure determination of the C. elegans IFT-B subcomplex, paired with an ontology term for structural constituent of the IFT particle.
Provenance (the field's own admissions):
Proposed term (ontology gap):
Gap: No independent biochemical or enzymatic activity has been demonstrated for OSM-6/IFT52, and although its N-terminal domain adopts a class-I glutamine-amidotransferase-like (GIFT) fold, whether this fold has any residual ligand-binding or catalytic role beyond scaffolding is unknown.
OPEN BIOLOGY MF_DARK
What is known: The GATase-like fold is annotated structurally (Pfam IFT52_GIFT / SSF52317); catalytic residues appear absent, consistent with a purely structural function.
Significance: Ruling in or out any ligand-binding role of the GIFT domain would clarify whether IFT52 does more than scaffold IFT-B.
What would resolve it: Structure-guided mutagenesis of the GIFT domain and in vitro binding/activity assays to test for retained ligand interaction.
Provenance (the field's own admissions):
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