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J. Biol. Chem., Vol. 283, Issue 19, 12981-12991, May 9, 2008

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GSK-3β Regulates Proper Mitotic Spindle Formation in Cooperation with a Component of the -Tubulin Ring Complex, GCP5^*

Nanae Izumi, Katsumi Fumoto, Shunsuke Izumi, and Akira Kikuchi¹

From the Department of Biochemistry, Graduate School of Biomedical Sciences, and Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan

Glycogen synthase kinase-3β (GSK-3β) is known to play a role in the regulation of the dynamics of microtubule networks in cells. Here we show the role of GSK-3β in the proper formation of the mitotic spindles through an interaction with GCP5, a component of the -tubulin ring complex (TuRC). GCP5 bound directly to GSK-3β in vitro, and their interaction was also observed in intact cells at endogenous levels. Depletion of GCP5 dramatically reduced the GCP2 and -tubulin in the TuRC fraction of sucrose density gradients and disrupted -tubulin localization to the spindle poles in mitotic cells. GCP5 appears to be required for the formation or stability of TuRC and the recruitment of -tubulin to the spindle poles. A GSK-3 inhibitor not only led to the accumulation of -tubulin and GCP5 at the spindle poles but also enhanced microtubule nucleation activity at the spindle poles. Depletion of GCP5 rescued this disrupted organization of spindle poles observed in cells treated with the GSK-3 inhibitor. Furthermore, the inhibition of GSK-3 enhanced the binding of TuRC to the centrosome isolated from mitotic cells in vitro. Our findings suggest that GSK-3β regulates the localization of TuRC, including GCP5, to the spindle poles, thereby controlling the formation of proper mitotic spindles.

Received for publication, December 18, 2007 , and in revised form, February 11, 2008.

^* This work was supported by grants-in-aid for scientific research and for scientific research on priority areas from the Ministry of Education, Science, and Culture, Japan (2005, 2006, and 2007). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S4.

¹ To whom correspondence should be addressed. Tel.: 81-82-257-5130; Fax: 81-82-257-5134; E-mail: akikuchi{at}hiroshima-u.ac.jp.

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