Taxol-induced flexibility of microtubules and its reversal by MAP-2 and Tau.
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.
Dye
R B
RB
Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235.
Fink
S P
SP
Williams
R C
RC
D000818:Animals; D004548:Elasticity; D066298:In Vitro Techniques; D008869:Microtubule-Associated Proteins / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D017239:Paclitaxel / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012617:Sea Urchins; D016875:tau Proteins / Q000494:pharmacology*
D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D017239:Paclitaxel