Molecular Biology of the Cell Sign up for new MBC in Press e-TOCs!

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print October 24, 2007
Mol. Biol. Cell 10.1091/mbc.E07-04-0371

A more recent version of this article appeared on January 1, 2008
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E07-04-0371v1
19/1/115    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fong, K.-W.
Right arrow Articles by Qi, R. Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fong, K.-W.
Right arrow Articles by Qi, R. Z.

Submitted on April 24, 2007
Revised on September 6, 2007
Accepted on October 16, 2007

CDK5RAP2 Is a Pericentriolar Protein That Functions in Centrosomal Attachment of the {gamma}-Tubulin Ring Complex

Ka-Wing Fong,* Yuk-Kwan Choi,* Jerome B. Rattner,{dagger} and Robert Z. Qi*

*Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; {dagger}Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta T2N 4N1, Canada

Monitoring Editor: Stephen Doxsey

Microtubule nucleation and organization by the centrosome require {gamma}-tubulin, a protein that exists in a macromolecular complex called the {gamma}-tubulin ring complex ({gamma}TuRC). We report characterization of CDK5RAP2, a novel centrosomal protein whose mutations have been linked to autosomal recessive primary microcephaly. In somatic cells, CDK5RAP2 localizes throughout the pericentriolar material in all stages of the cell cycle. When overexpressed, CDK5RAP2 assembled a subset of centrosomal proteins including {gamma}-tubulin onto the centrosomes or under the microtubule-disrupting conditions into microtubule-nucleating clusters in the cytoplasm. CDK5RAP2 associates with the {gamma}TuRC via a short conserved sequence present in several related proteins found in a range of organisms from fungi to mammals. The binding of CDK5RAP2 is required for {gamma}TuRC attachment to the centrosome but not for {gamma}TuRC assembly. Perturbing CDK5RAP2 function delocalized {gamma}-tubulin from the centrosomes and inhibited centrosomal microtubule nucleation, thus leading to disorganization of interphase microtubule arrays and formation of anastral mitotic spindles. Together, CDK5RAP2 is a pericentriolar structural component that functions in {gamma}TuRC attachment and therefore in the microtubule organizing function of the centrosome. Our findings suggest that centrosome malfunction due to the CDK5RAP2 mutations may underlie autosomal recessive primary microcephaly.

Address correspondence to: Robert Z. Qi (qirz{at}ust.hk)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.