MECHANISM OF MICROTUBULE DYNAMICS REGULATION BY KINESINS

描述（由申请人提供）：驱动蛋白是真核细胞骨架蛋白，以其运动活性而闻名，但它们也是微管（MT）动力学（MT聚合物生长或收缩的能力）的重要调节剂。本研究旨在探讨驱动蛋白超家族成员调控微管动力学的分子机制。这些驱动蛋白对MT动力学的调节在多种细胞过程中发挥重要作用，如有丝分裂、胞质分裂、神经发育以及纤毛和中心粒长度的控制，但这些驱动蛋白稳定或不稳定MT的机制尚不完全清楚。我们将测试的一般假设，即所有这些驱动蛋白影响MT的动力学通过修改微管蛋白的结构，有利于或不利于形成微管蛋白间的接触 将MT聚合物固定在一起。为了解决这一假设，我们将使用电子显微镜和其他方法来确定三个模型驱动蛋白的微管蛋白复合物的结构。该提案有两个总的目标。本研究的第一个目的是探讨驱动蛋白KLP 10A和Kar3对MT解聚的作用机制。第二个目标是通过驱动蛋白KIF14解决MT稳定的机制。

DESCRIPTION (provided by applicant): Kinesins are eukaryotic cytoskeletal proteins best known for their motile activity, but they are also important regulators of microtubule (MT) dynamics, the ability of the MT polymer to grow or shrink. This project seeks to establish the molecular mechanism of microtubule (MT) dynamics regulation by members of the kinesin superfamily. Regulation of MT dynamics by these kinesins play important roles in a variety of cell processes such as mitosis, cytokinesis, neural development and control of cilia and centriole length, but the mechanisms by which these kinesins stabilize or destabilize MTs are not fully clear. We will test the general hypothesis that all these kinesin affect MT-dynamics by modifying the structure of tubulin to favor or disfavor the formation of the inter-tubulin contacts that hold the MT polymer together. To address this hypothesis we will use electron microscopy and other approaches to determine the structure of tubulin complexes of three model kinesins. The proposal has two general aims. The fist aim is to establish the mechanism of MT depolymerization by the kinesins KLP10A and Kar3. The second aim addresses the mechanism of MT stabilization by the kinesin KIF14.