A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition
Francesc R. Garcia-Gonzalo,Kevin C. Corbit,María Salomé Sirerol-Piquer,Gokul Ramaswami,Edgar A. Otto,Thomas R. Noriega,Allen D. Seol,Jon F. Robinson,Christopher L. Bennett,Dragana Josifova,José Manuel García-Verdugo,Nicholas Katsanis,Friedhelm Hildebrandt,Friedhelm Hildebrandt,Jeremy F. Reiter +14 more
TLDR
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.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.read more
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Journal ArticleDOI
Genes and molecular pathways underpinning ciliopathies
TL;DR: Investigating ciliopathies has helped to understand the molecular mechanisms by which the cilium-associated basal body functions in early ciliogenesis, as well as how the transition zone functions in ciliary gating, and how intraflagellar transport enables cargo trafficking and signalling.
Journal ArticleDOI
Non-syndromic retinitis pigmentosa
Sanne K Verbakel,Ramon A. C. van Huet,Camiel J. F. Boon,Anneke I. den Hollander,Rob W.J. Collin,Caroline C W Klaver,Carel B. Hoyng,Ronald Roepman,B. Jeroen Klevering +8 more
TL;DR: A comprehensive overview of the clinical characteristics of RP specific to genetically defined patient subsets is provided, including a unique atlas with color fundus photographs of most RP subtypes, and the relevant considerations with respect to differential diagnoses are discussed.
Journal ArticleDOI
A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface.
Gagan D. Gupta,Etienne Coyaud,João Gonçalves,Bahareh A. Mojarad,Yi Liu,Yi Liu,Qianzhu Wu,Qianzhu Wu,Ladan Gheiratmand,David Comartin,David Comartin,Johnny M. Tkach,Sally W.T. Cheung,Mikhail Bashkurov,Monica Hasegan,James D.R. Knight,Zhen-Yuan Lin,Markus Schueler,Friedhelm Hildebrandt,Friedhelm Hildebrandt,Jason Moffat,Anne-Claude Gingras,Anne-Claude Gingras,Brian Raught,Brian Raught,Laurence Pelletier,Laurence Pelletier +26 more
TL;DR: Systematic profiling of proximity interactions combined with functional analysis provides a rich resource for better understanding human centrosome and cilia biology and may be applied to other complex biological structures or pathways.
Journal ArticleDOI
Primary Cilia and Mammalian Hedgehog Signaling.
Fiona Bangs,Kathryn V. Anderson +1 more
TL;DR: The genetic and developmental studies used to deduce how Hedgehog signal transduction is linked to cilia and the complex effects that perturbation of cilia structure can have on Hh signaling are summarized.
Journal ArticleDOI
The base of the cilium: roles for transition fibres and the transition zone in ciliary formation, maintenance and compartmentalization
TL;DR: Together with a recently described septin ring diffusion barrier at the ciliary base, the transition fibres and transition zone deserve attention for their varied roles in forming functional ciliary compartments.
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