Taxol induces microtubule assembly at low temperature.
Dissociated bovine brain microtubule protein has been shown to reassemble at 0 degrees C in the presence of the drug taxol. Tubulin polymerization was monitored both by electron microscopy of the polymeric structures and by incorporation of tritiated GTP into filterable polymeric structures. Most of the labeled guanine nucleotide uptake into tubulin polymeric structures occurred in the first 30 minutes of incubation with the drug. The initial polymerization event results in the formation of protofilamentous tubulin ribbons. The first microtubules were noted after 1 hour of incubation with the drug. After 20 hours of incubation at 0 degrees C with taxol, the bulk of the polymerized tubulin appeared to be in the form of microtubules. Cold-stable tubulin rings with a mean diameter of 34 nm were present in the reaction mixture before the addition of taxol and throughout the 20-hour incubation. Most of the rings were apparently not involved in the taxol-induced microtubule assembly. The results are consistent with a model whereby taxol induces an initial formation of protofilamentous ribbon structures, mostly from free tubulin dimers, and a slower subsequent folding of the ribbon structures into microtubules.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D003080:Cold Temperature; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure*; D017239:Paclitaxel; D014404:Tubulin / Q000378:metabolism*
D000470:Alkaloids; D046911:Macromolecular Substances; D014404:Tubulin; D006160:Guanosine Triphosphate; D017239:Paclitaxel