A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition
Top Cited Papers
Open Access
- 3 July 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 43 (8), 776-784
- https://doi.org/10.1038/ng.891
Abstract
Jeremy Reiter and colleagues show that Tctn1 is a component of a transition zone complex that regulates ciliogenesis and ciliary membrane composition. They also identify a likely causal mutation in TCTN1 in two siblings with Joubert syndrome. 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.Keywords
This publication has 50 references indexed in Scilit:
- Mapping the NPHP-JBTS-MKS Protein Network Reveals Ciliopathy Disease Genes and PathwaysCell, 2011
- Primary cilia regulate mTORC1 activity and cell size through Lkb1Nature, 2010
- Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathyNature Genetics, 2010
- Interaction and Localization of the Retinitis Pigmentosa Protein RP2 and NSF in Retinal Photoreceptor CellsBiochemistry, 2010
- The Conserved Bardet-Biedl Syndrome Proteins Assemble a Coat that Traffics Membrane Proteins to CiliaCell, 2010
- A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathiesNature Genetics, 2009
- Ciliary targeting motif VxPx directs assembly of a trafficking module through Arf4The EMBO Journal, 2009
- Mutations in the Cilia Gene ARL13B Lead to the Classical Form of Joubert SyndromeAmerican Journal of Human Genetics, 2008
- Vertebrate Smoothened functions at the primary ciliumNature, 2005
- Hedgehog signalling in the mouse requires intraflagellar transport proteinsNature, 2003