WDR93

WDR93 (FAP297/C1d-87/CFAP297) is a structural subunit of the C1d projection of the ciliary central apparatus, where it supports the motility functions of cilia and flagella (PMID:22573824). In Chlamydomonas, WDR93 assembles into the C1d projection alongside FAP54, FAP46, FAP74, and FAP221/Pcdp1, and loss of this projection disrupts flagellar motility, phototaxis, the photoshock response, and the control of interdoublet sliding velocity (PMID:22573824). Within the central-pair microtubules WDR93 also acts as an A-kinase anchoring protein (AKAP), associating with the RIIα-like protein FAP174 to form part of a PKA-anchoring signaling complex that couples the central apparatus to kinase signaling (PMID:38140814). Beyond its role as a conserved C1d projection component these mechanistic features have not been further characterized in the available corpus.

1. 2012 Medium

   Established WDR93 as a bona fide structural subunit of the ciliary central apparatus and tied the C1d projection it belongs to directly to flagellar motility control.

   Evidence Characterization of a Chlamydomonas fap46-1 null mutant lacking the C1d projection, with biochemical/structural identification of C1d-87 as a novel subunit and multiple motility readouts

   PMID:22573824

   Open questions at the time

   • Does not define WDR93's molecular activity or how it physically docks within C1d
   • Phenotypes derive from loss of the whole projection, not from WDR93-specific perturbation
   • No mammalian or vertebrate functional validation
2. 2023 Low

   Tested whether WDR93 is a conserved central-apparatus component across vertebrates by tracking its gene-disrupting loss alongside another C1d component.

   Evidence Comparative genomics across ~500 vertebrate genomes plus transcript analysis showing absence of WDR93 mRNA in bird lineages that concurrently lost CFAP46

   PMID:37621660

   Open questions at the time

   • Correlative genomic/transcript evidence with no direct functional reconstitution or mutagenesis
   • Mucociliary defence link is inferred, not experimentally demonstrated
   • Does not address WDR93 function in mammals
3. 2024 Medium

   Addressed how the central apparatus integrates kinase signaling by identifying WDR93 as an AKAP within a PKA-anchoring complex.

   Evidence Co-immunoprecipitation and mass spectrometry from enriched Chlamydomonas central-pair microtubule fractions using the RIIα-like FAP174 (RII D/D domain) as bait

   PMID:38140814

   Open questions at the time

   • Single method/single lab identification of the AKAP interaction
   • PKA-anchoring function not validated by functional or structural reconstitution
   • Downstream phosphorylation substrates of the anchored kinase unidentified

• How WDR93 mediates AKAP function and how its C1d structural role and PKA-anchoring role are mechanistically integrated to control ciliary beat remain unresolved.
• No structural model of WDR93 within the C1d projection
• No mammalian/human functional or disease characterization
• Mechanism linking PKA anchoring to interdoublet sliding velocity control undefined