Taxol-induced flexibility of microtubules and its reversal by MAP-2 and Tau.

Abstract

When microtubules, ordinarily quite rigid structures, are treated in vitro with the anti-tumor drug taxol, they rapidly develop a wavy appearance and become strikingly flexible. A quantitative measure of their flexibility, the reciprocal statistical length, lambda, increases by an order of magnitude when taxol is bound. Subsequent addition of either of the microtubule-associated proteins MAP-2 or tau causes the flexibility to disappear. It can be restored again by removing the microtubule-associated protein. These results show that taxol changes microtubular structure substantially, probably by weakening the interactions between protofilaments, and that microtubule-associated proteins reverse these effects, possibly by bridging protofilaments. This structural change and the accompanying flexibility may contribute importantly to taxol's cytotoxic activity.