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MBC in Press, published online ahead of print April 2, 2004
Mol. Biol. Cell 10.1091/mbc.E04-02-0082

A more recent version of this article appeared on June 1, 2004
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Submitted on February 2, 2004
Revised on March 11, 2004
Accepted on March 17, 2004

Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora B-dependent phosphorylation

Ryoma Ohi1*, Tanuj Sapra2, Jonathan Howard2, and Timothy J. Mitchison3

1 Department of Systems Biology, Harvard Medical School, Boston, MA, 02115
2 Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
3 Department of Systems Biology, Harvard Medical School, Boston, MA, 02115. Institute for Chemistry and Cell Biology, Harvard Medical School, Boston, MA, 02115

* Corresponding author. E-mail address: ryoma ohi{at}hms.harvard.edu.

The KinI kinesin MCAK is a microtubule depolymerase important for governing spindle microtubule dynamics during chromosome segregation. The dynamic nature of spindle assembly and chromosome-microtubule interactions suggest that mechanisms must exist that modulate the activity of MCAK, both spatially and temporally. In Xenopus extracts, MCAK associates with and is stimulated by the inner centromere protein ICIS. The inner centromere kinase Aurora B also interacts with ICIS and MCAK raising the possibility that Aurora B may regulate MCAK activity as well. Herein, we demonstrate that recombinant Aurora B-INCENP inhibits Xenopus MCAK activity in vitro in a phosphorylation-dependent manner. Substituting endogenous MCAK in Xenopus extracts with the alanine mutant XMCAK-4A, which is resistant to inhibition by Aurora B-INCENP, led to assembly of mono-astral and monopolar structures instead of bipolar spindles. The size of these structures and extent of tubulin polymerization in XMCAK-4A extracts indicate that XMCAK-4A is not defective for microtubule dynamics regulation throughout the cytoplasm. We further demonstrate that the ability of XMCAK-4A to localize to inner centromeres is abolished. Our results show that MCAK regulation of cytoplasmic and spindle-associated microtubules can be differentiated by Aurora B-dependent phosphorylation, and they further demonstrate that this regulation is required for bipolar meiotic spindle assembly.






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