DIFFERENTIAL-EFFECTS OF VINBLASTINE ON POLYMERIZATION AND DYNAMICS ATOPPOSITE MICROTUBULE ENDS

We have characterized the effects of vinblastine on the growing and sh ortening dynamics at opposite ends of individual bovine brain microtub ules at steady state in vitro by video microscopy. Vinblastine exerted strikingly different effects on the dynamics and polymer mass at the plus and minus ends of microtubules. At concentrations between 0.1 and 0.4 mu M, the drug strongly depolymerized microtubules at minus ends, whereas it did not significantly depolymerize microtubules at plus en ds, Vinblastine stabilized plus ends by suppressing the rate and exten t of growth and shortening, decreasing the catastrophe frequency, and increasing the rescue frequency, In contrast, vinblastine destabilized minus ends by increasing the catastrophe frequency and decreasing the rescue frequency, whereas it had no effect on the rate or extent of g rowth or shortening, Thus, vinblastine moderately increased the overal l dynamicity at minus ends while strongly suppressing dynamicity at pl us ends. Both the kinetic destabilization of microtubules at minus end s and the stabilization at plus ends may contribute to the altered fun ction of mitotic spindle Microtubules of cells blocked in mitosis by l ow concentrations of vinblastine.