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

TitleCEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium.
Publication TypeJournal Article
Year of Publication2012
AuthorsLee, JE, Silhavy JL, Zaki MS, Schroth J, Bielas SL, Marsh SE, Olvera J, Brancati F, Iannicelli M, Ikegami K, Schlossman AM, Merriman B, AttiƩ-Bitach T, Logan CV, Glass IA, Cluckey A, Louie CM, Lee JH, Raynes HR, Rapin I, Castroviejo IP, Setou M, Barbot C, Boltshauser E, Nelson SF, Hildebrandt F, Johnson CA, Doherty DA, Valente EM, Gleeson JG
JournalNature genetics
Volume44
Issue2
Pagination193-9
Date Published2012 Feb
ISSN1546-1718
KeywordsAnimals, Centrosome, Cerebellar Diseases, Chromosome Mapping, Cilia, Ciliary Motility Disorders, Eye Abnormalities, Female, Genetic Loci, Glutamic Acid, Humans, Male, Mice, Mutation, Peptide Synthases, Polycystic Kidney Diseases, Polymorphism, Single Nucleotide, Protein Processing, Post-Translational, Proteins, Syndrome, Tubulin
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.

DOI10.1111/j.1465-3362.2010.00271.x
Alternate JournalNat. Genet.