1. Academic Validation
  2. CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium

CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium

  • Nat Genet. 2012 Jan 15;44(2):193-9. doi: 10.1038/ng.1078.
Ji Eun Lee 1 Jennifer L Silhavy Maha S Zaki Jana Schroth Stephanie L Bielas Sarah E Marsh Jesus Olvera Francesco Brancati Miriam Iannicelli Koji Ikegami Andrew M Schlossman Barry Merriman Tania Attié-Bitach Clare V Logan Ian A Glass Andrew Cluckey Carrie M Louie Jeong Ho Lee Hilary R Raynes Isabelle Rapin Ignacio P Castroviejo Mitsutoshi Setou Clara Barbot Eugen Boltshauser Stanley F Nelson Friedhelm Hildebrandt Colin A Johnson Daniel A Doherty Enza Maria Valente Joseph G Gleeson
Affiliations

Affiliation

  • 1 Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California, USA.
Abstract

Tubulin glutamylation is a post-translational modification that occurs predominantly in the ciliary axoneme and has been suggested to be important for ciliary function. However, its relationship to disorders of the primary cilium, termed ciliopathies, has not been explored. Here we mapped a new locus for Joubert syndrome (JBTS), which we have designated as JBTS15, and identified causative mutations in CEP41, which encodes a 41-kDa centrosomal protein. We show that CEP41 is localized to the basal body and primary cilia, and regulates ciliary entry of TTLL6, an evolutionarily conserved polyglutamylase Enzyme. Depletion of CEP41 causes ciliopathy-related phenotypes in zebrafish and mice and results in glutamylation defects in the ciliary axoneme. Our data identify CEP41 mutations as a cause of JBTS and implicate tubulin post-translational modification in the pathogenesis of human ciliary dysfunction.

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