DRUG INTERACTIONS WITH BRAIN MICROTUBULE 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，如发展和 维持细胞形状和各种细胞内运动 (e.g.,减数分裂过程中轴突内运输和有丝分裂染色体运动 和有丝分裂）。 微管群体在细胞中是不同的， 完全稳定的，如在纤毛和鞭毛中发现的， 非常动态的，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多种聚合作用 体外的行为，可能反映了他们的异质性行为， 在细胞中展示。 细胞可以使用聚合物的各种聚合能力。 微管来完成不同的功能。 似乎有理由 认为微管的功能，如那些相关的 细胞中微管的组织和生长，以及与 某些类型的微管连接运动，如有丝分裂染色体， 运动，通过组件机械地确定和调节， 和微管末端的分解反应。 进一步说， 认为微管行为和功能的多样性 不同的微管蛋白和微管相关蛋白的参与 在不同的微管群体中。 因此，本提案的主要策略是研究 微管蛋白添加和微管末端的损失。 的组合 将采用能够区分微管蛋白添加和缺失的程序 个别微管末端的动力学，以及电子显微镜分析 微管长度动力学的显微镜。 微管制剂 由不同的微管蛋白和微管相关蛋白组成， 将检查大脑和海胆卵和精子。 目标是 了解负责微管蛋白的增加和损失的机制， 微管末端，并识别，表征和理解 分子的功能与表面和末端相互作用， 微管和调节组装和拆卸动力学细胞。

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.