The mechanisms of action of the "catastrophe kinesins": Kinesins that destabilize the ends of microtubules

目前的研究方案涉及运动蛋白的一个亚家族的作用机制，即所谓的破坏微管末端稳定的“灾难运动蛋白”。这些动蛋白通过与微管末端结合来控制微管种群的长度和分布，但对它们的作用机制知之甚少。我们的团队和其他人已经建立了检测微管末端在生长和收缩之间变化的结构变化的方法。这项工作导致了稳定不断增长的微管的结构帽的概念。2)结果表明，微管种群的长度由突变激动素XKCM1和稳定微管的MAP XMAP215的相反活性控制。在未发表的工作中，我们进一步证明了这两种蛋白质在调节纯微管蛋白的生长过程中可以相互对立。在这个项目中，我们建议a)通过冷冻电子显微镜将微管末端的结构与XKCM1的活性相关联。B)研究XKCM1的活性是如何受xMAP 215的活性调节的。

The present research proposal is concerned with the mechanisms of action of a sub-family of the kinesins, the so-called "catastrophe-kinesins" which destabilize the ends of microtubules. These kinesins are essential for controlling the length and distribution of microtubule populations, by binding to microtubule ends, but little is know of their mechanism of action. Our group and others have 1) Established assays which examine the structural changes of microtubule ends during the change between growing and shrinking. This work has lead to the concept of a structural cap stabilizing growing microtubules. 2) Shown that the length of a microtubule population is controlled by the opposing activity of XKCM1, a catastrophe kinesin, and XMAP215, a MAP which stabilizes microtubules. In unpublished work, we have further shown the two proteins can oppose each other in the regulation of the growth of pure tubulin. In this project we propose to a) Correlate the structure of the microtubule end with the activity of XKCM1, by cryoelectron microscopy. b) To investigate how the activity of XKCM1 is modulated by the activity of XMAP 215.