CEP162 is an axoneme-recognition protein promoting ciliary transition zone assembly at the cilia base

Nat Cell Biol. 2013 Jun;15(6):591-601. doi: 10.1038/ncb2739. Epub 2013 May 5.

Abstract

The transition zone is a specialized compartment found at the base of cilia, adjacent to the centriole distal end, where axonemal microtubules are heavily crosslinked to the surrounding membrane to form a barrier that gates the ciliary compartment. A number of ciliopathy molecules have been found to associate with the transition zone, but factors that directly recognize axonemal microtubules to specify transition zone assembly at the cilia base remain unclear. Here, through quantitative centrosome proteomics, we identify an axoneme-associated protein, CEP162 (KIAA1009), tethered specifically at centriole distal ends to promote transition zone assembly. CEP162 interacts with core transition zone components, and mediates their association with microtubules. Loss of CEP162 arrests ciliogenesis at the stage of transition zone assembly. Abolishing its centriolar tethering, however, allows CEP162 to stay on the growing end of the axoneme and ectopically assemble transition zone components at cilia tips. This generates extra-long cilia with strikingly swollen tips that actively release ciliary contents into the extracellular environment. CEP162 is thus an axoneme-recognition protein pre-tethered at centriole distal ends before ciliogenesis to promote and restrict transition zone formation specifically at the cilia base.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3 Cells
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Axoneme / metabolism*
  • Cell Line
  • Centrioles / metabolism*
  • Centrosome / metabolism
  • Cilia / metabolism*
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism
  • Mice
  • Microtubule Proteins / genetics
  • Microtubule Proteins / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Proteomics
  • RNA Interference
  • RNA, Small Interfering

Substances

  • Antigens, Neoplasm
  • Cep290 protein, human
  • Membrane Proteins
  • Microtubule Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • Adenosine Triphosphatases
  • KIAA1009 protein, human