A Transition Zone Complex Regulates Mammalian Ciliogenesis and Ciliary Membrane Composition

By Francesc R. Garcia-Gonzalo, K. Corbit, M. Sirerol-Piquer, Gokul Ramaswami, E. Otto, Thomas R. Noriega, Allen D. Seol, Jon F. Robinson, C. L. Bennett, D. Josifova and 4 more. Nature Genetics, 2011

654 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b267325195df10a2603c9747157a17942db4b16f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

Citations in the corpus

The Gene Ontology of eukaryotic cilia and flagella (2017, background): “For instance, many proteins involved in ciliopathies are located in particular ciliary substructures, such as the transition zone for Meckel-Gruber and Joubert syndromes [12] and the BBSome complex for Bardet-Biedl syndrome [13].”