daf-10

UniProt ID: G5EFW7
Organism: Caenorhabditis elegans
Review Status: COMPLETE
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Gene Description

DAF-10 is the Caenorhabditis elegans ortholog of human IFT122, a core subunit of intraflagellar transport complex A (IFT-A). It is a large (1192 aa) WD40 Ξ²-propeller plus tetratricopeptide-repeat (TPR) solenoid scaffold with a C-terminal zinc-ribbon and no catalytic domain, expressed in ciliated sensory neurons and shuttling along the axoneme of the non-motile sensory cilium at the same rate as IFT-B proteins. As part of IFT-A, DAF-10 is required for retrograde (ciliary tip-to-base) intraflagellar transport powered by cytoplasmic dynein-2, and thereby for assembly and maintenance of the sensory-cilium axoneme and for import of ciliary membrane cargo such as G protein-coupled receptors. Loss of DAF-10 produces structurally defective, disorganized sensory cilia with the characteristic IFT-A retrograde-defect signature (accumulation of IFT-B/OSM-6 material in the ciliary endings), together with dye-filling and chemotaxis defects. Because worm sensory cilia detect environmental cues, daf-10 mutants are dauer-formation-defective (the origin of the gene name, abnormal DAuer Formation) and show altered sensory modulation of insulin/IGF and TGF-Ξ² signaling. IFT122 mutations cause human ciliopathies (cranioectodermal dysplasia / Sensenbrenner syndrome), underscoring a conserved role in cilium biogenesis.

Proposed New Ontology Terms

structural constituent of intraflagellar transport particle

Definition: The action of a protein that contributes to the structural integrity of an intraflagellar transport (IFT) particle (IFT-A or IFT-B subcomplex), for example by acting as a WD40/TPR scaffold that holds core IFT subunits together and enables their bidirectional transport along the ciliary axoneme, without itself catalyzing a biochemical reaction.

Parent term: structural molecule activity

Existing Annotations Review

GO Term Evidence Action Reason
GO:0061512 protein localization to cilium
IBA
GO_REF:0000033
ACCEPT
Summary: As an IFT-A subunit, DAF-10 transports and localizes protein cargo along the ciliary axoneme; loss of daf-10 disrupts the distribution of IFT-B (OSM-6) material in the ciliary endings.
Reason: Core process. Phylogenetic inference agrees with the founding paper, which established daf-10 as an IFT gene mediating the bidirectional movement of particles along the ciliary axoneme (i.e. protein localization within the cilium).
Supporting Evidence:
PMID:16648645
Some genes in this category are known to be required for intraflagellar transport (IFT), which is the bidirectional movement of raft-like particles along the axonemes of cilia and flagella
GO:0035721 intraciliary retrograde transport
IBA
GO_REF:0000033
ACCEPT
Summary: As a core IFT-A subunit, DAF-10 is required for retrograde (tip-to-base) intraflagellar transport, the defining function of IFT-A.
Reason: Represents the core biological process of the gene. Phylogenetic inference is corroborated by the IFT-A/retrograde-defect phenotype of daf-10 mutants and by mass-spec placement of DAF-10 in the worm IFT-A complex.
Supporting Evidence:
PMID:28479320
Cytoplasmic dynein-2 powers retrograde intraflagellar transport that is essential for cilium formation and maintenance
GO:0097730 non-motile cilium
IBA
GO_REF:0000033
ACCEPT
Summary: DAF-10 acts within the worm's non-motile sensory cilia, where it shuttles along the axoneme as part of IFT-A.
Reason: Core localization, accurately specific to the worm's non-motile sensory cilia. Phylogenetic inference agrees with the direct ciliary localization of DAF-10 (IFT shuttling in amphid/phasmid cilia) and with the mutant cilia phenotype.
GO:1905515 non-motile cilium assembly
IBA
GO_REF:0000033
ACCEPT
Summary: IFT-A/retrograde transport by DAF-10 is required to build and maintain the non-motile sensory-cilium axoneme; loss of daf-10 gives structurally defective cilia.
Reason: Core process, accurately specific for the worm's non-motile sensory cilia. Phylogenetic inference is corroborated by the ciliogenesis defect of daf-10 mutants.
Supporting Evidence:
PMID:21124868
daf-10/IFT122 mutations (which disrupt ciliogenesis)
GO:0030991 intraciliary transport particle A
IBA
GO_REF:0000033
ACCEPT
Summary: DAF-10 is a core subunit of the IFT-A complex, established by orthology to IFT122 and by direct mass-spec identification in the worm IFT-A complex.
Reason: Core complex membership. Phylogenetic inference agrees with the experimental (NAS/mass-spec, ISS) IFT-A assignments; the founding paper notes that the WAA-repeat architecture shared by daf-10 is characteristic of IFT particle components.
Supporting Evidence:
PMID:16648645
The daf-10 and osm-1 gene products resemble each other and contain WD and WAA repeats
IEA
GO_REF:0000044
ACCEPT
Summary: Electronic (UniProt SubCell) assertion of ciliary localization, redundant with the more specific non-motile cilium annotation.
Reason: Correct location; consistent with the direct evidence that DAF-10 shuttles along sensory cilia, albeit less specific than the non-motile cilium term.
GO:0060271 cilium assembly
IEA
GO_REF:0000120
ACCEPT
Summary: Electronic (ARBA/InterPro) annotation of the IFT-A cilium-assembly role, redundant with the experimental IGI/IMP and phylogenetic annotations.
Reason: Correct core process; consistent with the ciliogenesis defect of daf-10 mutants, though less specific than the non-motile cilium assembly term.
NAS
PMID:28479320
Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...
ACCEPT
Summary: ComplexPortal (CPX-1289) NAS assertion of ciliary localization for the IFT-A complex, based on the mass-spec study of worm retrograde IFT.
Reason: Correct core localization, consistent with the direct ciliary shuttling of DAF-10.
GO:0030991 intraciliary transport particle A
NAS
PMID:28479320
Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...
ACCEPT
Summary: ComplexPortal NAS annotation placing DAF-10 in the IFT-A complex, based on affinity purification / mass spectrometry of the worm IFT-A complex (che-11, daf-10, dyf-2, ift-139, ift-43, ifta-1).
Reason: Core complex membership, experimentally grounded (mass-spec definition of the worm IFT-A complex, which includes DAF-10).
Supporting Evidence:
PMID:28479320
our affinity purification and genetic analyses show that IFT-A
GO:0035721 intraciliary retrograde transport
NAS
PMID:28479320
Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...
ACCEPT
Summary: ComplexPortal NAS annotation of the IFT-A retrograde-transport role.
Reason: Core process, consistent with the experimental and phylogenetic evidence for DAF-10 as a retrograde IFT-A subunit.
Supporting Evidence:
PMID:28479320
Cytoplasmic dynein-2 powers retrograde intraflagellar transport that is essential for cilium formation and maintenance
GO:0060271 cilium assembly
NAS
PMID:28479320
Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...
ACCEPT
Summary: ComplexPortal NAS annotation of the cilium-assembly role of IFT-A.
Reason: Correct; downstream outcome of the IFT-A transport function and consistent with the ciliogenesis defect of daf-10 mutants.
GO:0030991 intraciliary transport particle A
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence-similarity (ISS) transfer of IFT-A membership from the human ortholog IFT122 (Q9HBG6).
Reason: Core complex membership; the ISS to human IFT122 agrees with the direct mass-spec IFT-A assignment in the worm.
GO:0036064 ciliary basal body
IDA
PMID:27623382
A Conserved Role for Girdin in Basal Body Positioning and Ci...
ACCEPT
Summary: Direct-assay assertion of DAF-10 at the ciliary basal body, from a study of Girdin-dependent basal-body positioning and ciliogenesis.
Reason: Biologically consistent location: IFT-A proteins concentrate at the ciliary base / transition-fibre region before axonemal entry. Retained as a genuine location per repo guidance not to overrule an experimental IDA; the cached record is abstract-only and does not name daf-10, so the datum is deferred to the curator's full-text reading (see reference_review). A secondary/base localization rather than the core axonemal-transport function.
GO:0061065 regulation of dauer larval development
IGI
PMID:21124868
Localization of a guanylyl cyclase to chemosensory cilia req...
KEEP AS NON CORE
Summary: Genetic interaction with daf-25/Ankmy2: daf-10 loss (disrupting ciliogenesis) suppresses the daf-25 dauer-constitutive phenotype, implicating daf-10 in the chemosensory control of dauer formation.
Reason: Valid genetic-interaction phenotype, but a downstream consequence of the ciliary/IFT defect (functional chemosensory cilia are required to sense the dauer cues), not a core molecular function of an IFT-A structural subunit.
Supporting Evidence:
PMID:21124868
daf-10/IFT122 mutations (which disrupt ciliogenesis)
GO:0060271 cilium assembly
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
ACCEPT
Summary: daf-10 is among the dauer-defective genes whose mutations cause structurally defective chemosensory cilia, implicating it in building the sensory cilium.
Reason: Core process; the cilium-structure defect of daf-10 mutants directly supports a requirement in ciliary assembly/maintenance.
Supporting Evidence:
PMID:1732156
structurally defective chemosensory cilia
GO:0061066 positive regulation of dauer larval development
IMP
PMID:6583682
A pheromone-induced developmental switch in Caenorhabditis e...
KEEP AS NON CORE
Summary: daf-10 is required for dauer formation (loss-of-function is dauer-defective), so it positively regulates entry into the dauer larval stage; the classic dauer-pheromone-switch study frames dauer-defective mutants as unresponsive to pheromone.
Reason: Well-established phenotype (the gene is named for abnormal DAuer Formation), but a downstream sensory consequence of the ciliary defect rather than a core molecular function. The cached record is abstract-only and does not name daf-10; retained per guidance not to overrule the WormBase IMP.
Supporting Evidence:
PMID:6583682
Dauer-defective mutants fail to respond to added pheromone
GO:0097500 receptor localization to non-motile cilium
IMP
PMID:24646679
Diverse cell type-specific mechanisms localize G protein-cou...
ACCEPT
Summary: daf-10 is required for correct ciliary localization of G protein-coupled receptors in sensory neurons, reflecting the IFT-A role in ciliary import of membrane cargo.
Reason: A specific, well-grounded manifestation of IFT-A function: import/retention of ciliary membrane GPCRs depends on intact IFT. The cached record is abstract-only and does not name daf-10; retained per guidance not to overrule the WormBase IMP and because the requirement is consistent with the established IFT-A role in ciliary GPCR trafficking.
Supporting Evidence:
PMID:24646679
localize GPCRs to the cilia of the AWB and ASK sensory neuron types
GO:1905515 non-motile cilium assembly
IMP
PMID:16648645
The molecular identities of the Caenorhabditis elegans intra...
ACCEPT
Summary: Mutant analysis in the founding paper: daf-10 (complex A) is required for proper sensory-cilium structure; loss abnormally redistributes OSM-6::GFP in the ciliary endings.
Reason: Core process, accurately specific for the worm's non-motile sensory cilia and supported by the mutant phenotype. daf-10 is one of the IFT genes cloned in this paper whose loss perturbs sensory-cilium structure.
Supporting Evidence:
PMID:16648645
The daf-10 and osm-1 gene products resemble each other and contain WD and WAA repeats
GO:0046626 regulation of insulin receptor signaling pathway
IGI
PMID:11381260
Regulation of the Caenorhabditis elegans longevity protein D...
KEEP AS NON CORE
Summary: Sensory (ciliated) neurons modulate DAF-16/insulin-IGF signaling systemically; daf-10 contributes to this via a genetic interaction, reflecting the sensory input of the ciliary system into insulin signaling.
Reason: Indirect, whole-organism sensory-modulation effect (ciliary sensory neurons influence DAF-16 nuclear localization), not a molecular function of an IFT-A structural subunit. Retained as a legitimate genetic-interaction phenotype but marked non-core/downstream.
Supporting Evidence:
PMID:11381260
both sensory neurons and germline activity regulate DAF-16 accumulation in nuclei

Core Functions

Structural constituent of intraflagellar transport complex A (IFT-A) that drives retrograde (ciliary tip-to-base) intraflagellar transport along the non-motile sensory cilium. As the IFT122 ortholog, DAF-10 has no catalytic activity; it acts as a WD40/TPR/Zn-ribbon scaffold within IFT-A that, with cytoplasmic dynein-2, returns IFT particles and turnover products from the ciliary tip to the base.

Supporting Evidence:
  • PMID:16648645
    The daf-10 and osm-1 gene products resemble each other and contain WD and WAA repeats
  • PMID:28479320
    IFT-139 and IFT-43 function redundantly to promote dynein-2 motility

Required for assembly and maintenance of the non-motile sensory cilium and for ciliary import of membrane cargo. IFT-A function via DAF-10 is needed to build and maintain the ciliary axoneme, to keep IFT-B/ciliary proteins correctly distributed, and to localize signaling receptors (GPCRs) to the ciliary compartment; loss of DAF-10 disrupts ciliogenesis.

Supporting Evidence:

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Suggested Questions for Experts

Q: What is the subunit-resolved architecture of the C. elegans IFT-A complex, and which IFT-A subunits does DAF-10/IFT122 directly contact?

Suggested experts: Ou G

Q: Which ciliary phenotypes (retrograde IFT, axoneme assembly, ciliary GPCR import) are specifically attributable to DAF-10 versus the IFT-A complex as a whole?

Suggested experts: Sengupta P

Suggested Experiments

Experiment: Affinity-purify or reconstitute the worm IFT-A complex and determine its architecture by cryo-EM, assigning DAF-10/IFT122 and its direct neighbors and testing whether ciliopathy-mimicking substitutions perturb specific interfaces.

Hypothesis: DAF-10/IFT122 occupies a defined position within an IFT-A scaffold that can be resolved structurally.

Type: structural biology

Experiment: Generate structure-guided separation-of-function alleles of daf-10 and score, in vivo, retrograde IFT (kymography of IFT-B markers), cilium length, and ciliary localization of tagged GPCRs in AWB/ASK neurons, to test whether cargo-import and transport functions can be genetically uncoupled.

Hypothesis: DAF-10 makes a separable contribution to ciliary GPCR import distinct from its role in bulk retrograde IFT.

Type: structure-function mutagenesis

Knowledge Gaps

What is not known β€” curated, literature-grounded statements of the open unknowns (the inverse of core functions).

Gap: DAF-10 has no molecular-function annotation and no GO term that can express one. Its role is to be a structural constituent of the IFT-A particle, but GO has no "structural constituent of the intraflagellar transport particle" molecular-function term, so the gene reads as MF-dark despite a well-understood cellular and process-level role.

OPEN ONTOLOGYCURATION MF_DARK

What is known: It is firmly established that DAF-10 = IFT122 is a WD40+TPR+Zn-ribbon scaffolding subunit of IFT-A with no catalytic domain, required for retrograde IFT and cilium assembly. What is missing is a molecular-function representation: the worm GOA record carries only cellular-component and biological-process terms and no molecular_function annotation at all.

Significance: This is the canonical "structural subunit" ontology gap: a mechanistically well-understood protein that cannot be annotated with an informative MF term, contributing to apparent molecular-function darkness across the IFT/ciliopathy gene set (the same gap affects dyf-2/WDR19 and other IFT-A/IFT-B subunits).

What would resolve it: Develop/adopt a molecular-function term for a structural constituent of the IFT particle (analogous to "structural constituent of ribosome"), then annotate DAF-10 (and other IFT-A/IFT-B core subunits) to it.

Provenance (the field's own admissions):

Proposed term (ontology gap):

Gap: The subunit-resolved architecture of the C. elegans IFT-A complex, and which of DAF-10's ciliary functions (retrograde transport, axoneme assembly, GPCR import) are directly and specifically mediated by DAF-10 versus emerging from IFT-A as a whole, are not dissected. DAF-10's direct IFT-A neighbor contacts are inferred from cross-species orthology and worm mass-spec composition, not resolved structurally.

OPEN BIOLOGY RESIDUAL_SUBGAP

What is known: The worm IFT-A composition (che-11, daf-10, dyf-2, ift-139, ift-43, ifta-1) is known from affinity purification / mass spectrometry, and daf-10 loss produces the IFT-A retrograde-defect signature (IFT-B accumulation in ciliary endings). What is not known is the position of DAF-10/IFT122 within a solved IFT-A structure, its direct binding partners in the worm, and any DAF-10-specific (as opposed to complex-level) contribution to cargo selection.

Significance: IFT-A subunit architecture determines how retrograde IFT is organized and how ciliopathy-causing IFT122 mutations perturb it; a DAF-10-resolved structure and separation-of-function alleles would explain which ciliary phenotypes are directly attributable to DAF-10.

What would resolve it: Cryo-EM of the worm IFT-A complex with DAF-10/IFT122 assigned, plus structure-guided separation-of-function alleles scored in vivo for retrograde IFT (kymography of IFT-B markers), cilium length, and ciliary GPCR localization.

Provenance (the field's own admissions):

Tags

caeel-ciliopathy

πŸ“š Additional Documentation

Notes

(daf-10-notes.md)

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