VINBLASTINE SUPPRESSES DYNAMICS OF INDIVIDUAL MICROTUBULES IN LIVING INTERPHASE CELLS
VINBLASTINE SUPPRESSES DYNAMICS OF INDIVIDUAL MICROTUBULES IN LIVING INTERPHASE CELLS
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DOI：
10.1091/mbc.6.9.1215
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发表时间：
1995-09-01
影响因子：
3.3
通讯作者：
WADSWORTH, P
中科院分区：
文献类型：
--
作者：
DHAMODHARAN, R;JORDAN, MA;WADSWORTH, P
我们已经表征了长春碱对用罗丹明标记的微管蛋白显微注射的活BS-C-1细胞中单个微管的动态不稳定行为的影响，并且发现在低浓度（3-64 nM）下，长春碱有效地抑制动态不稳定性而不引起净微管解聚。长春碱抑制微管生长和缩短的速率，并降低从生长或暂停到缩短的转变频率，也称为灾难。在长春碱处理的细胞中，暂停的平均持续时间（一种既不能检测到生长也不能检测到缩短的衰减动力学状态）和暂停总时间的百分比均显著增加。长春碱有效地降低了动态性，这是微管整体动态活性的一个指标，在32 nM时，该参数降低了75%。目前的工作，与早期的体外研究一致，表明长春碱动力学帽的微管在活细胞中的末端，并支持的假设，即长春碱作为一种抗肿瘤药物的有效的化疗作用是抑制有丝分裂纺锤体微管动力学。此外，结果表明，结合到微管末端的分子可以调节活细胞中的微管动力学行为，并表明通过类似机制工作的微管动力学的内源性调节剂可能存在于活细胞中。
We have characterized the effects of vinblastine on the dynamic instability behavior of individual microtubules in living BS-C-1 cells microinjected with rhodamine-labeled tubulin and have found that at low concentrations (3-64 nM), vinblastine potently suppresses dynamic instability without causing net microtubule depolymerization. Vinblastine suppressed the rates of microtubule growth and shortening, and decreased the frequency of transitions from growth or pause to shortening, also called catastrophe. In vinblastine-treated cells, both the average duration of a pause (a state of attenuated dynamics where neither growth nor shortening could be detected) and the percentage of total time spent in pause were significantly increased. Vinblastine potently decreased dynamicity, a measure of the overall dynamic activity of microtubules, reducing this parameter by 75% at 32 nM. The present work, consistent with earlier in vitro studies, demonstrates that vinblastine kinetically caps the ends of microtubules in living cells and supports the hypothesis that the potent chemotherapeutic action of vinblastine as an antitumor drug is suppression of mitotic spindle microtubule dynamics. Further, the results indicate that molecules that bind to microtubule ends can regulate microtubule dynamic behavior in living cells and suggest that endogenous regulators of microtubule dynamics that work by similar mechanisms may exist in living cells.