Modulation of microtubule dynamics by drugs: a paradigm for the actions of cellular regulators

Cell Structure and Function
L WilsonM A Jordan

Abstract

Microtubules are intrinsically dynamic polymers. Two kinds of dynamic behaviors, dynamic instability and treadmilling, are important for microtubule function in cells. Both dynamic behaviors appear to be tightly regulated, but the cellular molecules and the mechanisms responsible for the regulation remain largely unexplored. While microtubule dynamics can be modulated transiently by the interaction of regulatory molecules with soluble tubulin, the microtubule itself is likely to be the primary target of cellular molecules that regulate microtubule dynamics. The antimitotic drugs that modulate microtubule dynamics serve as excellent models for such cellular molecules. Our laboratory has been investigating the interactions of small drug molecules and stabilizing microtubule-associated proteins (MAPs) with microtubule surfaces and ends. We find that drugs such as colchicine, vinblastine, and taxol, and stabilizing MAPs such as tau, strongly modulate microtubule dynamics at extremely low concentrations under conditions in which the microtubule polymer mass is minimally affected. The powerful modulation of the dynamics is brought about by the binding of only a few drug or MAP molecules to distinct binding sites at the microtubule su...Continue Reading

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Citations

Jul 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Dulal PandaLeslie Wilson
Jan 18, 2005·The Journal of Biological Chemistry·Adam I MarcusParaskevi Giannakakou
Dec 3, 2005·Learning & Memory·Radmila MileusnicSteven P R Rose
Apr 11, 2009·The Journal of Biological Chemistry·Tapas MannaLeslie Wilson
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