A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition

Francesc R. Garcia-Gonzalo, Kevin C. Corbit, Maré Salomé Sirerol-Piquer, Gokul Ramaswami, Edgar A. Otto, Thomas R. Noriega, Allen D. Seol, Jon F. Robinson, Christopher L. Bennett, Dragana J. Josifova, José Manuel García-Verdugo, Elias Nicholas Katsanis, Friedhelm Hildebrandt, Jeremy F. Reiter*

*Corresponding author for this work

Research output: Contribution to journalArticle

354 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)776-784
Number of pages9
JournalNature Genetics
Volume43
Issue number8
DOIs
StatePublished - Aug 2011

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition'. Together they form a unique fingerprint.

  • Cite this

    Garcia-Gonzalo, F. R., Corbit, K. C., Sirerol-Piquer, M. S., Ramaswami, G., Otto, E. A., Noriega, T. R., Seol, A. D., Robinson, J. F., Bennett, C. L., Josifova, D. J., García-Verdugo, J. M., Katsanis, E. N., Hildebrandt, F., & Reiter, J. F. (2011). A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. Nature Genetics, 43(8), 776-784. https://doi.org/10.1038/ng.891