A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition
Por:
F. GARCIA-GONZALO, K. CORBIT, M. SIREROL-PIQUER, G. RAMASWAMI, E. OTTO, T. NORIEGA, A. SEOL, J. ROBINSON, C. BENNETT, D. JOSIFOVA, J. GARCIA-VERDUGO, N. KATSANIS, F. HILDEBRANDT and J. REITER
Publicada:
1 ago 2011
Resumen:
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.
Filiaciones:
F. GARCIA-GONZALO:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
K. CORBIT:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
M. SIREROL-PIQUER:
Univ Valencia, Lab Morfol Celular, Unidad Mixta Ctr Invest Principe Felipe, Ctr Invest Biomed Red CIBERNED, Valencia, Spain
G. RAMASWAMI:
Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
E. OTTO:
Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
T. NORIEGA:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
A. SEOL:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
J. ROBINSON:
Duke Univ, Dept Cell Biol, Ctr Human Dis Modeling, Durham, NC USA
Duke Univ, Dept Pediat, Durham, NC 27706 USA
C. BENNETT:
Duke Univ, Dept Cell Biol, Ctr Human Dis Modeling, Durham, NC USA
Duke Univ, Dept Pediat, Durham, NC 27706 USA
D. JOSIFOVA:
Guys Hosp, Dept Clin Genet, London SE1 9RT, England
:
Univ Valencia, Lab Morfol Celular, Unidad Mixta Ctr Invest Principe Felipe, Ctr Invest Biomed Red CIBERNED, Valencia, Spain
Univ Valencia, Cavanilles Inst Biodivers & Evolutionary Biol, Dept Comparat Neurobiol, Valencia, Spain
N. KATSANIS:
Duke Univ, Dept Cell Biol, Ctr Human Dis Modeling, Durham, NC USA
Duke Univ, Dept Pediat, Durham, NC 27706 USA
F. HILDEBRANDT:
Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
Howard Hughes Med Inst, Chevy Chase, MD USA
J. REITER:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
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