The CP110-interacting proteins Talpid3 and Cep290 play overlapping and distinct roles in cilia assembly

J Cell Biol. 2014 Jan 20;204(2):215-29. doi: 10.1083/jcb.201304153. Epub 2014 Jan 13.

Abstract

We have identified Talpid3/KIAA0586 as a component of a CP110-containing protein complex important for centrosome and cilia function. Talpid3 assembles a ring-like structure at the extreme distal end of centrioles. Ablation of Talpid3 resulted in an aberrant distribution of centriolar satellites involved in protein trafficking to centrosomes as well as cilia assembly defects, reminiscent of loss of Cep290, another CP110-associated protein. Talpid3 depletion also led to mislocalization of Rab8a, a small GTPase thought to be essential for ciliary vesicle formation. Expression of activated Rab8a suppressed cilia assembly defects provoked by Talpid3 depletion, suggesting that Talpid3 affects cilia formation through Rab8a recruitment and/or activation. Remarkably, ultrastructural analyses showed that Talpid3 is required for centriolar satellite dispersal, which precedes the formation of mature ciliary vesicles, a process requiring Cep290. These studies suggest that Talpid3 and Cep290 play overlapping and distinct roles in ciliary vesicle formation through regulation of centriolar satellite accretion and Rab8a.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism
  • Antigens, Neoplasm / physiology*
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / physiology*
  • Centrioles / metabolism
  • Cilia / metabolism*
  • Cilia / ultrastructure
  • Cytoskeletal Proteins
  • Green Fluorescent Proteins / analysis
  • HEK293 Cells
  • Humans
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / physiology*
  • Recombinant Fusion Proteins / analysis
  • rab GTP-Binding Proteins / analysis
  • rab GTP-Binding Proteins / metabolism

Substances

  • Antigens, Neoplasm
  • Cell Cycle Proteins
  • Cep290 protein, human
  • Cytoskeletal Proteins
  • KIAA0586 protein, human
  • Neoplasm Proteins
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • RAB8A protein, human
  • rab GTP-Binding Proteins