Catalytic modulation of microtubule polymerization: A molecular and biochemical dissection

微管聚合的催化调节：分子和生化剖析

• 批准号: RGPIN-2015-04103
• 负责人: Kwok, Benjamin
• 金额: $ 2.19万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=683373
• 关键词: Catalytic; modulation; microtubule; polymerization; molecular

When a cell divides, it duplicates the genetic material within and packages them into chromosomes. Microtubules are essential "cable-like" protein polymers that need to be assembled into a multi-component machine called the mitotic apparatus to search and capture these chromosomes and distribute them equally into the resulting two daughter cells. We know that microtubules work by adding and removing their building blocks, tubulin, to make them grow or shrink. This dynamic property is very important for their functions. Recently, we have found that a protein called KIF14 not only can bind to microtubules, but can actually promote the assembly of microtubules. This gives us an opportunity to take a closer look into the molecular mechanism of how microtubule assembly or polymerization can be enhanced by KIF14. We propose to use biochemical and high-resolution imaging techniques to examine KIF14-induced microtubule polymerization. This effort aims to provide a glimpse of what could be happening in the microtubule network during cell division, and more fundamentally the regulated process of microtubule assembly. Ultimately, the proposed research will tell us more about the rather mysterious and complex control of polymer systems in a very important process - cell division. It will contribute to a deeper understanding of the molecular mechanism underlying microtubule polymer assembly.

当细胞分裂时，它复制内部的遗传物质并将它们包装成染色体。 微管是必不可少的“电缆状”蛋白质聚合物，需要组装成一个多组件机器，称为有丝分裂装置，以搜索和捕获这些染色体，并将它们均匀地分配到产生的两个子细胞中。 我们知道微管通过添加和移除它们的构建模块微管蛋白来使它们生长或收缩。 这种动态特性对它们的功能非常重要。 最近，我们发现一种名为KIF 14的蛋白质不仅可以与微管结合，而且实际上可以促进微管的组装。 这使我们有机会更仔细地研究KIF 14如何增强微管组装或聚合的分子机制。 我们建议使用生物化学和高分辨率成像技术来检查KIF 14诱导的微管聚合。 这项工作的目的是提供一个什么可能发生在细胞分裂过程中的微管网络一瞥，更根本的是微管组装的调节过程。 最终，拟议中的研究将告诉我们更多关于聚合物系统在一个非常重要的过程中相当神秘和复杂的控制-细胞分裂。 这将有助于更深入地了解微管聚合物组装的分子机制。