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

Tapas Manna 1 Douglas Thrower 1 Herbert Miller 1 Patrick Curmi 2 Leslie Wilson 1
1 MCDB-UCSB - Department of Molecular, Cellular and Develomental Biology [Santa Barbara]
2 LSRB - Laboratoire Structure et Reconnaissance des Biomolécules, EA3637, Université Evry-Val d’Essonne
Abstract : Stathmin is a ubiquitous microtubule destabilizing protein that isbelieved to play an important role linking cell signaling to the reg-ulation of microtubule dynamics. Here we show that stathminstrongly destabilizes microtubule minus endsin vitroat steadystate, conditions in which the soluble tubulin and microtubule lev-els remain constant. Stathmin increased the minus end catastrophefrequency13-fold at a stathmin:tubulin molar ratio of 1:5. Stath-min steady-state catastrophe-promoting activity was considerablystronger at the minus ends than at the plus ends. Consistent with itsability to destabilize minus ends, stathmin strongly increased thetreadmilling rate of bovine brain microtubules. By immunofluores-cence microscopy, we also found that stathmin binds to purifiedmicrotubules along their lengthsin vitro. Co-sedimentation of puri-fied microtubules polymerized in the presence of a 1:5 initial molarratio of stathmin to tubulin yielded a binding stoichiometry of 1 molof stathmin per14.7 mol of tubulin in the microtubules. Theresults firmly establish that stathmin can increase the steady-statecatastrophe frequency by a direct action on microtubules, and fur-thermore, they indicate that an important regulatory action ofstathmin in cells may be to destabilize microtubule minus ends.
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Submitted on : Tuesday, September 24, 2019 - 11:50:29 AM
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Tapas Manna, Douglas Thrower, Herbert Miller, Patrick Curmi, Leslie Wilson. Stathmin Strongly Increases the Minus End Catastrophe Frequency and Induces Rapid Treadmilling of Bovine Brain Microtubules at Steady State in Vitro. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2006, 281 (4), pp.2071-2078. ⟨10.1074/jbc.M510661200⟩. ⟨hal-02295524⟩

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