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J. Biol. Chem., Vol. 281, Issue 4, 2071-2078, January 27, 2006

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Stathmin Strongly Increases the Minus End Catastrophe Frequency and Induces Rapid Treadmilling of Bovine Brain Microtubules at Steady State in Vitro^*

Tapas Manna1, Douglas Thrower1, Herbert P. Miller, Patrick Curmi, and Leslie Wilson2

From the Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106 and Laboratoire Structure et Reconnaissance des Biomolécules, EA3637, Université Evry-Val d'Essonne, rue du père Jarlan, 91025 Evry, France

Stathmin is a ubiquitous microtubule destabilizing protein that is believed to play an important role linking cell signaling to the regulation of microtubule dynamics. Here we show that stathmin strongly destabilizes microtubule minus ends in vitro at steady state, conditions in which the soluble tubulin and microtubule levels remain constant. Stathmin increased the minus end catastrophe frequency 13-fold at a stathmin:tubulin molar ratio of 1:5. Stathmin steady-state catastrophe-promoting activity was considerably stronger at the minus ends than at the plus ends. Consistent with its ability to destabilize minus ends, stathmin strongly increased the treadmilling rate of bovine brain microtubules. By immunofluorescence microscopy, we also found that stathmin binds to purified microtubules along their lengths in vitro. Co-sedimentation of purified microtubules polymerized in the presence of a 1:5 initial molar ratio of stathmin to tubulin yielded a binding stoichiometry of 1 mol of stathmin per 14.7 mol of tubulin in the microtubules. The results firmly establish that stathmin can increase the steady-state catastrophe frequency by a direct action on microtubules, and furthermore, they indicate that an important regulatory action of stathmin in cells may be to destabilize microtubule minus ends.

Received for publication, September 29, 2005 , and in revised form, November 11, 2005.

^* This work was supported by United States Public Health Service Grant NS13560 (to L. W.) and a Genopole® Actualités de la Génomique et des Biotechnologies grant (to P. C.). 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 material.

¹ These authors contributed equally to this work.

² To whom correspondence should be addressed. Tel.: 805-893-2819; Fax: 805-893-8094; E-mail: Wilson{at}lifesci.ucsb.edu.

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