2. Academic Validation
  3. 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.
PMID: 22246503 DOI: 10.1038/ng.1078
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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