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MBC in Press, published online ahead of print June 13, 2007
Mol. Biol. Cell 10.1091/mbc.E07-01-0086

A more recent version of this article appeared on September 1, 2007
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Submitted on February 1, 2007
Revised on May 24, 2007
Accepted on June 5, 2007

Aurora B Phosphorylates Multiple Sites on MCAK to Spatially and Temporally Regulate Its Function

Xin Zhang,* Weijie Lan,{dagger} Stephanie C. Ems-McClung,{ddagger} P. Todd Stukenberg,{dagger} and Claire E. Walczak{ddagger}

*Department of Biology, Indiana University, Bloomington, IN 47405; {dagger}Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA 22908; {ddagger}Department of Biochemistry and Molecular Biology, Indiana University Medical Sciences, Bloomington, IN 47405

Monitoring Editor: Ted Salmon

Chromosome congression and segregation require the proper attachment of microtubules to the two sister kinetochores. Disruption of either Aurora B kinase or the Kinesin-13 MCAK increases chromosome misalignment and missegregation due to improper kinetochore-microtubule attachments. MCAK localization and activity are regulated by Aurora B, but how Aurora B phosphorylation of MCAK affects spindle assembly is unclear. Here we show that the binding of MCAK to chromosome arms is also regulated by Aurora B, and that Aurora B dependent chromosome arm and centromere localization is regulated by distinct two-site phospho-regulatory mechanisms. MCAK association with chromosome arms is promoted by phosphorylation of T95 on MCAK, while phosphorylation of S196 on MCAK promotes dissociation from the arms. Whereas targeting of MCAK to centromeres requires phosphorylation of S110 on MCAK, dephosphorylation of T95 on MCAK increases the binding of MCAK to centromeres. Our studies reveal a new role for Aurora B, which is to prevent excess MCAK binding to chromatin to facilitate chromatin-nucleated spindle assembly. Our studies also show that the interplay between multiple phosphorylation sites of MCAK may be critical to temporally and spatially control MCAK function.

Address correspondence to: Claire E. Walczak (cwalczak{at}indiana.edu)




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