TALPID3 and ANKRD26 selectively orchestrate FBF1 localization and cilia gating

Nat Commun. 2020 May 4;11(1):2196. doi: 10.1038/s41467-020-16042-w.

Abstract

Transition fibers (TFs) regulate cilia gating and make the primary cilium a distinct functional entity. However, molecular insights into the biogenesis of a functional cilia gate remain elusive. In a forward genetic screen in Caenorhabditis elegans, we uncover that TALP-3, a homolog of the Joubert syndrome protein TALPID3, is a TF-associated component. Genetic analysis reveals that TALP-3 coordinates with ANKR-26, the homolog of ANKRD26, to orchestrate proper cilia gating. Mechanistically, TALP-3 and ANKR-26 form a complex with key gating component DYF-19, the homolog of FBF1. Co-depletion of TALP-3 and ANKR-26 specifically impairs the recruitment of DYF-19 to TFs. Interestingly, in mammalian cells, TALPID3 and ANKRD26 also play a conserved role in coordinating the recruitment of FBF1 to TFs. We thus report a conserved protein module that specifically regulates the functional component of the ciliary gate and suggest a correlation between defective gating and ciliopathy pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Animals, Genetically Modified
  • Basal Bodies / metabolism
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cells, Cultured
  • Centrioles / metabolism
  • Cilia / genetics
  • Cilia / metabolism*
  • HEK293 Cells
  • Humans
  • Microscopy, Confocal
  • Mutation
  • RNA Interference
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins