DRUG INTERACTIONS WITH BRAIN MICROTUBLE PROTEINS

微管是真核生物细胞骨架的重要组成部分 细胞，并参与不同的过程，如发育和 维持细胞形态和各种细胞内运动 (例如，减数分裂过程中的轴突内运输和有丝分裂染色体运动 和有丝分裂)。微管群体在细胞上不同，从 完全稳定，如在纤毛和鞭毛中发现的那些 极具活力的，如在有丝分裂和减数分裂纺锤体中发现的那些。 已经发现微管表现出各种聚合作用。 在体外的行为可能反映了他们的异质行为 在细胞中展示。细胞可以使用各种聚合功能 微管完成不同的功能。这似乎是合理的 相信微管功能，如那些与 细胞中微管的组织和生长，以及与之相关的那些 某些类型的微管连接的运动，如有丝分裂染色体 运动，通过装配机械地确定和调节 以及微管末端的拆解反应。此外，这也是合理的 认为微管行为和功能的多样性可能与 不同的微管蛋白和微管相关蛋白的参与 在不同的微管种群中。 因此，这项提议的主要战略是调查 微管蛋白在体外微管末端的添加和丢失。一种组合 将采用能够区分微管蛋白增加和丢失的程序 单个微管末端的动力学与电子分析 微管长度动力学的显微镜观察。微管制剂 由不同的微管蛋白和微管相关蛋白组成 将检查大脑和海胆的卵子和精子。我们的目标是 了解微管蛋白增加和丢失的机制 微管末端，并识别、表征和理解微管 与表面和末端相互作用的分子的功能 微管和调节细胞内的组装和拆卸动力学。

Microtubules are important components of the cytoskeleton of eucaryotic cells, and participate in diverse processes such as the development and maintenance of cell shape and in various kinds of intracellular movements (e.g., intraaxonal transport and mitotic chromosome movement during meiosis and mitosis). Microtubule populations differ in cells, from being completely stable such as those found in cilia and flagella, to being extremely dynamic, such as those found in mitotic and meiotic spindles. Microtubules have been found to exhibit a variety of polymerization behaviors in vitro that may reflect the heterogeneous behaviors that they exhibit in cells. Cells may use the various polymerization capabilities of microtubules to accomplish different functions. It seems reasonable to believe that microtubule functions such as those related to the organization and growth of microtubules in cells, and those associated with certain kinds of microtubule-linked motility such as mitotic chromosome movement, are mechanistically determined and regulated through the assembly and disassembly reactions at microtubule ends. Further, it is reasonable to think that diversity in microtubule behavior and function may be related to participation of distinct tubulins and microtubule-associated proteins in different microtubule populations. Thus, the main strategy of this proposal is to investigate the dynamics of tubulin addition and loss at microtubule ends in vitro. A combination of procedures will be employed that can distinguish tubulin addition and loss dynamics at individual microtubule ends, together with analysis by electron microscopy of microtubule length dynamics. Microtubule preparations composed of distinct tubulins and microtubule-associated proteins from brain and sea urchin eggs and sperm will be examined. The goal is to understand the mechanisms responsible for tubulin addition and loss at microtubule ends, and to identify, characterize, and understand the functions of molecules that interact with the surfaces and ends of microtubules and regulate assembly and disassembly dynamics in cells.