Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Nature genetics | Feb 27, 2012

http://www.ncbi.nlm.nih.gov/pubmed/22246503

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.

Pubmed ID: 22246503 RIS Download

Mesh terms: Animals | 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

Research resources used in this publication

None found

Research tools detected in this publication

Data used in this publication

None found

Associated grants

  • Agency: Medical Research Council, Id: G0700073
  • Agency: Telethon, Id: GGP08145
  • Agency: NICHD NIH HHS, Id: P01 HD070494
  • Agency: NICHD NIH HHS, Id: P01 HD070494-02
  • Agency: NINDS NIH HHS, Id: P30 NS047101
  • Agency: NINDS NIH HHS, Id: P30 NS047101-10
  • Agency: NINDS NIH HHS, Id: P30NS047101
  • Agency: NIDDK NIH HHS, Id: R01 DK068306
  • Agency: NINDS NIH HHS, Id: R01 NS048453
  • Agency: NINDS NIH HHS, Id: R01 NS048453-08
  • Agency: NINDS NIH HHS, Id: R01 NS052455
  • Agency: NINDS NIH HHS, Id: R01 NS052455-06
  • Agency: NINDS NIH HHS, Id: R01 NS064077
  • Agency: NIDDK NIH HHS, Id: R01DK068306
  • Agency: NINDS NIH HHS, Id: R01NS048453
  • Agency: NINDS NIH HHS, Id: R01NS052455
  • Agency: NINDS NIH HHS, Id: R01NS064077
  • Agency: NCRR NIH HHS, Id: S10 RR029130
  • Agency: NCRR NIH HHS, Id: S10 RR029130-01
  • Agency: NIGMS NIH HHS, Id: T32 GM008666
  • Agency: Howard Hughes Medical Institute, Id:

ZFIN (Data, Gene Expression)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.