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Vol. 19, Issue 7, 2752-2765, July 2008

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E08-02-0198v1 19/7/2752    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Zhang, X. Articles by Walczak, C. E. PubMed PubMed Citation Articles by Zhang, X. Articles by Walczak, C. E.

Aurora A Phosphorylates MCAK to Control Ran-dependent Spindle Bipolarity

Departments of Biochemistry and Molecular Biology, and Medical Sciences, Indiana University, Bloomington, IN 47405

Submitted February 25, 2008; Revised March 31, 2008; Accepted April 10, 2008
Monitoring Editor: Stephen Doxsey

During mitosis, mitotic centromere-associated kinesin (MCAK) localizes to chromatin/kinetochores, a cytoplasmic pool, and spindle poles. Its localization and activity in the chromatin region are regulated by Aurora B kinase; however, how the cytoplasmic- and pole-localized MCAK are regulated is currently not clear. In this study, we used Xenopus egg extracts to form spindles in the absence of chromatin and centrosomes and found that MCAK localization and activity are tightly regulated by Aurora A. This regulation is important to focus microtubules at aster centers and to facilitate the transition from asters to bipolar spindles. In particular, we found that MCAK colocalized with NuMA and XMAP215 at the center of Ran asters where its activity is regulated by Aurora A-dependent phosphorylation of S196, which contributes to proper pole focusing. In addition, we found that MCAK localization at spindle poles was regulated through another Aurora A phosphorylation site (S719), which positively enhances bipolar spindle formation. This is the first study that clearly defines a role for MCAK at the spindle poles as well as identifies another key Aurora A substrate that contributes to spindle bipolarity.

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

Abbreviations used: GFP, green fluorescent protein; MCAK, mitotic centromere-associated kinesin; MT, microtubule; Ran, ras-related nuclear protein.

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