CFAP184

CFAP184 (CCDC96) is an axonemal protein that contributes to the structural and regulatory architecture governing ciliary motility (PMID:33661892). It forms a stable complex with CCDC113 that localizes parallel to the nexin-dynein regulatory complex (N-DRC) in the ciliary axoneme, physically connecting radial spoke 3 (RS3) to dynein g and the N-DRC; while CFAP184 and CCDC113 can each be transported to cilia independently, stable docking and function require both subunits (PMID:33661892). Structural analysis places this complex in close contact with DRC9/10 in the linker region of the N-DRC (PMID:37714832). Deletion of CFAP184 alters ciliary beat frequency, amplitude, and waveform, consistent with a role in transmitting regulatory signals from RS3 and the N-DRC to dynein g to coordinate motility (PMID:33661892). An earlier proteomic and localization study also placed CCDC96 at the centrosome in cultured mammalian cells (PMID:25074808).

1. 2014 Medium

   Established a first subcellular foothold for an uncharacterized coiled-coil protein by identifying it in centriole-associated proteomes, raising the question of its functional role at microtubule-based structures.

   Evidence Mass spectrometry of sperm centrioles with fluorescence localization in cultured mammalian cells

   PMID:25074808

   Open questions at the time

   • Single lab, single localization method for CCDC96
   • No functional role assigned
   • No binding partners identified
2. 2021 High

   Resolved CFAP184's molecular role by showing it forms a CCDC113-dependent complex bridging radial spoke 3 to dynein g and the N-DRC, and that its loss disrupts ciliary beating — establishing it as a regulatory link in the axonemal motility machinery.

   Evidence Genetic deletion, cryo-electron tomography, co-immunoprecipitation, and cilia beating assays

   PMID:33661892

   Open questions at the time

   • Precise mechanism by which the signal is transmitted to dynein g not defined
   • Stoichiometry of the CFAP184/CCDC113 complex unresolved
   • How independent transport to cilia is coordinated into stable docking unknown
3. 2023 High

   Refined the structural placement of the complex by showing the CCDC96/CCDC113 module contacts DRC9/10 in the N-DRC linker region, anchoring its proposed regulatory connection in molecular detail.

   Evidence Cryo-electron microscopy with biochemical cross-linking and integrative modeling in Tetrahymena thermophila

   PMID:37714832

   Open questions at the time

   • Single study and single organism
   • Functional consequence of the DRC9/10 contact not tested by perturbation
   • Atomic-resolution model of the interface not established

• How CFAP184 mechanically transduces RS3/N-DRC regulatory cues into modulation of dynein g activity, and whether its centrosomal localization reflects a distinct non-ciliary function, remain unresolved.
• No direct demonstration of signal transduction to dynein g activity
• Relationship between centrosomal and axonemal localizations unexplained
• No human disease association established in the corpus