A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition.

Published online

Journal Article

Mutations affecting ciliary components cause ciliopathies. As described here, we investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and found that it is essential for ciliogenesis in some, but not all, tissues. Cell types that do not require Tctn1 for ciliogenesis require it to localize select membrane-associated proteins to the cilium, including Arl13b, AC3, Smoothened and Pkd2. Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. Components of this complex co-localize at the transition zone, a region between the basal body and ciliary axoneme. Like Tctn1, loss of Tctn2, Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary membrane composition. Consistent with a shared function for complex components, we identified a mutation in TCTN1 that causes Joubert syndrome. Thus, a transition zone complex of Meckel and Joubert syndrome proteins regulates ciliary assembly and trafficking, suggesting that transition zone dysfunction is the cause of these ciliopathies.

Full Text

Cited Authors

  • Garcia-Gonzalo, FR; Corbit, KC; Sirerol-Piquer, MS; Ramaswami, G; Otto, EA; Noriega, TR; Seol, AD; Robinson, JF; Bennett, CL; Josifova, DJ; García-Verdugo, JM; Katsanis, N; Hildebrandt, F; Reiter, JF

Published Date

  • July 3, 2011

Published In

Volume / Issue

  • 43 / 8

Start / End Page

  • 776 - 784

PubMed ID

  • 21725307

Pubmed Central ID

  • 21725307

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.891

Language

  • eng

Conference Location

  • United States