DYNAMICS OF CENTROSOME/MICROTUBULE ASSOCIATION

描述：父提案的总体目标 FIRCA是为了了解体内和体外的微管动力学， 特别是，为了确定相互之间的耦合的性质 染色体运动和微管的生长和缩短。特定的 本赠款期间的目标侧重于分析 微管的形成、分解、周转和选择性 稳定状态。待研究的细胞系统包括哺乳动物 成纤维细胞、有丝分裂细胞和神经元。这项提案针对的是 MT动力学领域的明显悖论。虽然是动态的 不稳定性现在被确立为MT周转的主要机制， 考虑到体外和体内的全部证据表明 这种动态的不稳定性，就像最初的公式一样，无法解释 体内周转的速度。需要检验的具体假设 在这个提案中，是中心体的“传送带组装”模型 活动由外国合作者于1983年首次提出。根据 在这种观点下，MT阵列是通过在以下位置启动MTS来开发的 中心体之后是他们的分离(释放)和向心性 从中心体移位。对经济增长的两个关键预测 将对输送机装配模型进行测试：(I)减去MTS的端部 培养的细胞比较稳定；(Ii)MTS连续 从中心体中释放出来。

DESCRIPTION: The broad objectives of the parent proposal for this FIRCA are to understand microtubule dynamics in vivo and in vitro and, in particular, to determine the nature of the coupling between chromosome movement and microtubule growth and shortening. Specific aims targeted in the current grant period focus on analysis of microtubule formation, disassembly, turnover, and selective stabilization. Cell systems to be investigated include mammalian fibroblasts, mitotic cells, and neurons. This proposal addresses an apparent paradox in the MT dynamics field. Although dynamic instability is now established as a primary mechanism of MT turnover, consideration of the totality of evidence in vitro and in vivo suggests that dynamic instability, as originally formulated, cannot account for the rapidity of turnover in vivo. The specific hypothesis to be tested in this proposal is the "conveyor assembly" model for centrosome activity first proposed by the foreign collaborator in 1983. According to this view, the MT array is developed by initiation of MTs at the centrosome followed by their detachment (release) and centripetal displacement away from the centrosome. Two key predictions of the conveyor assembly model will be tested: (i) minus ends of MTs in cultured cells are rather stable; and (ii) MTs are continuously released from the centrosome.