IFT-43 is the Caenorhabditis elegans ortholog of IFT43, the smallest subunit of intraflagellar transport complex A (IFT-A). It is a short (200 aa) protein with no known catalytic domain. IFT-43 is expressed in ciliated sensory neurons, localizes to the sensory cilium and co-purifies with IFT-A. On its own, loss of ift-43 causes no obvious defect in cilium morphology. IFT-43 acts redundantly with the IFT-A subunit IFT-139: ift-139; ift-43 double mutants have defective cilia, and the two proteins together promote motility of the retrograde motor dynein-2 (CHE-3). IFT-43 is also one of the IFT-A subunits, with IFTA-1 and IFT-139, needed to remove periciliary membrane proteins from the cilium (transition-zone gating). Human IFT43 mutations cause cranioectodermal dysplasia and retinal dystrophy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping placing IFT-43 in the cilium. Reason: Correct. UniProt records ciliary localization from PMID:28479320, and IFT-43 is an IFT-A subunit that travels on IFT trains. Supporting Evidence: file:worm/ift-43/ift-43-uniprot.txt SUBCELLULAR LOCATION: Cell projection, cilium |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal (IFT-A complex) assertion that IFT-43 localizes to the cilium. Reason: Correct and consistent with the UniProt-recorded ciliary localization. |
| GO:0030991 intraciliary transport particle A | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal complex-membership assertion that IFT-43 is part of IFT-A. Reason: Core complex membership. IFT43 is a conserved IFT-A subunit, and the paper's affinity purification associates worm IFT-43 with IFT-A. Supporting Evidence: PMID:28479320 our affinity purification and genetic analyses show that IFT-A subunits IFT-139 and IFT-43 function redundantly to promote dynein-2 motility |
| GO:0035721 intraciliary retrograde transport | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal assertion that IFT-A, including IFT-43, mediates retrograde IFT. Reason: Core process. The paper shows IFT-43 promotes dynein-2 motility, redundantly with IFT-139. Because of that redundancy the single mutant shows little defect, but the double mutant shows the role. Supporting Evidence: PMID:28479320 our affinity purification and genetic analyses show that IFT-A subunits IFT-139 and IFT-43 function redundantly to promote dynein-2 motility |
| GO:0060271 cilium assembly | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal assertion that IFT-A, including IFT-43, is needed for cilium assembly. Reason: Supported, with a caveat. ift-43 single mutants have normally shaped cilia, but ift-139; ift-43 double mutants have defective cilia. IFT-43 therefore contributes to cilium assembly through IFT-A, with IFT-139 covering for it. Supporting Evidence: file:worm/ift-43/ift-43-uniprot.txt No visible phenotype, with no defects in cilium morphology. Double knockout with intraflagellar transport protein ift-139 results in defective cilium morphology and function. |
Loading supporting content…
Download this section (compressed HTML)Q: Does worm IFT-43 bridge IFT-121/IFTA-1 and IFT-139 in the IFT-A2 lobe, as in other species, and is that why its loss is masked when IFT-139 is present?
Experiment: Image periciliary membrane cargo and dynein-2 in ift-43 single mutants and in ift-43; ift-139 double mutants, at single-molecule resolution.
Hypothesis: IFT-43 is needed to remove membrane cargo from the cilium but is dispensable for retrograde motor coupling when IFT-139 is present.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: What IFT-43 does on its own is unknown. It is dispensable for cilium shape when IFT-139 is present, yet it is needed to clear periciliary membrane proteins from cilia. Whether this reflects a distinct cargo-handling role or only a weakened IFT-A2 lobe has not been tested.
OPEN BIOLOGY
What is known: Established: IFT-A membership, redundancy with IFT-139 for dynein-2 motility and cilium morphology, and a role in ciliary gating. Unknown: the direct partners of IFT-43 in the worm and the mechanism of its gating role.
Significance: IFT43 is mutated in human ciliopathies even though the worm single mutant has nearly normal cilia; knowing its separable role would help interpret those alleles.
What would resolve it: Single-molecule imaging of IFT-A, dynein-2 and periciliary membrane cargo in ift-43 single and ift-43; ift-139 double mutants, plus binding assays between IFT-43 and IFT-121/IFTA-1 and IFT-139.
Provenance (the field's own admissions):
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)