Related Experiment Videos
Taxol-induced flexibility of microtubules and its reversal by MAP-2 and Tau
R B Dye1, S P Fink, R C Williams
1Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235.
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.
Insights
The anti-tumor drug taxol significantly increases microtubule flexibility by altering their structure. Microtubule-associated proteins (MAPs) can reverse this taxol-induced flexibility, impacting drug activity.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Microtubules are rigid cytoskeletal polymers essential for cell structure and division.
- The anti-tumor drug taxol is known to interact with microtubules.
- Microtubule-associated proteins (MAPs) regulate microtubule dynamics and stability.
Purpose of the Study:
- To investigate the effect of taxol on microtubule flexibility.
- To determine the role of MAP-2 and tau in modulating taxol's effects on microtubules.
- To elucidate the structural basis for taxol's impact on microtubule mechanics.
Main Methods:
- In vitro treatment of microtubules with taxol.
- Quantitative measurement of microtubule flexibility using reciprocal statistical length (lambda).
- Addition and removal of microtubule-associated proteins (MAP-2 and tau).
Main Results:
- Taxol treatment induced a significant increase (order of magnitude) in microtubule flexibility.
- MAP-2 and tau binding abolished taxol-induced flexibility.
- Removal of MAPs restored the increased flexibility.
- Taxol likely weakens protofilament interactions, while MAPs bridge them.
Conclusions:
- Taxol substantially alters microtubule structure, increasing their flexibility.
- MAPs counteract taxol's effects by stabilizing microtubule protofilament interactions.
- The taxol-induced structural changes and flexibility may be crucial for its cytotoxic activity.