Article

A Transition Zone Complex Regulates Mammalian Ciliogenesis and Ciliary Membrane Composition

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA.
Nature Genetics (Impact Factor: 29.65). 07/2011; 43(8):776-84. DOI: 10.1038/ng.891
Source: PubMed

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.

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Available from: Dragana J Josifova, Jul 29, 2015
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    • "The transition zone, which has been proposed to regulate the entry and exit of proteins and protein complexes into the ciliary axoneme (Craige et al., 2010; Ishikawa and Marshall, 2011), lies between the centriolar appendages and the ciliary axoneme. MKS1 and TMEM67, components of a large protein complex at the transition zone (Dowdle et al., 2011; Garcia-Gonzalo et al., 2011), were correctly localized to the mother centriole in Ttbk2 bby mutant cells (Figures 3C, 3D, S3C, and S3D). Thus, these components of the mature basal body assembled correctly in the absence of TTBK2, despite a failure of axoneme elongation. "
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