Gamma-Tubulin And Centrosome Structure And Function

描述(逐字摘自申请者的摘要)：长期目标 这一建议的目的是了解微管组织的分子基础 中心函数，这是产生极微管所必需的 细胞骨架执行染色体分离的重要任务，细胞 运动性、细胞器运输和核迁移。我们才刚刚开始 来回答这个领域的一些核心问题：组织是如何 中心是微管生长的核心？如何在时间上成核和成核 空间上受控制的？哪些分子对细胞内的哪些功能起重要作用 组织中心？癌细胞的微管组织常有缺陷 中心的大小和数量，可能导致遗传不稳定，证明 这些问题的重要性。为了加深我们对 微管组织中心(动物细胞中称为中心体)我会 主要关注γ-微管蛋白和大分子的结构和功能 它是大分子组件的一部分，即γ-微管蛋白复合体(也称为 伽马-微管蛋白环复合体，或伽马-TURC)。γ-微管蛋白复合体是 微管成核所需的，并已被提议作为直接的 微管聚合的模板。γ-微管蛋白复合体是 由γ-微管蛋白和五种不同的多肽组成。这一非凡之处 复合体必须同时与微管和中心体相互作用，将其放置在 微管组织的中心。我们发现这五个人 γ-微管蛋白复合体，又称GCP，属于一个新的蛋白质超家族。 伽马微管蛋白在微管组织中的重要性使我们 在哺乳动物基因组中寻找新的微管蛋白，我们发现了两个， D(Delta)-微管蛋白和e(Epsilon)-微管蛋白。Epsilon微管蛋白尚未被描述 以前在任何有机体中，它的性质表明在中心体中起到了作用 功能也是如此。我们将在下一个项目期实现四个具体目标： 1)确定γ-微管蛋白的亚基组成和结构 很复杂。2)确定γ-微管蛋白复合体蛋白之间的相互作用， 以及它们在伽马-微管蛋白复合体中的作用。3)描述 具有微管和中心体的γ-微管蛋白复合体。4) 表征epsilon-微管蛋白在中心体功能中的作用。

DESCRIPTION (Verbatim from the applicant's abstract): The long term objective of this proposal is to understand the molecular basis of microtubule organizing center function, which is essential to generating a polar microtubule cytoskeleton to carry out the important tasks of chromosome segregation, cell motility, organelle transport, and nuclear migration. We have only just begun to answer some of the central questions in this field: How does the organizing center nucleate the growth of microtubules? How is nucleation temporally and spatially regulated? Which molecules are important for which functions in the organizing center? Cancer cells often have defects in microtubule organizing center size and number, possibly leading to genetic instability, demonstrating the importance of these questions. To further our understanding of the microtubule organizing center (called the centrosome in animal cells) I will focus primarily on the structure and function of gamma-tubulin and the large macromolecular assembly of which it is part, gamma-tubulin complex (also called the gamma-tubulin ring complex, or gamma-TuRC). The gamma-tubulin complex is required for microtubule nucleation, and has been proposed to act as a direct template for the polymerization of microtubules. The gamma-tubulin complex is made up of gamma-tubulin plus five different polypeptides. This remarkable complex must interact both with microtubules and the centrosome, placing it at the center of microtubule organization. We have found that all five of the gamma-tubulin complex proteins, or GCPs, belong to a new protein superfamily. The importance of gamma-tubulin in microtubule organization has led us to search for new tubulins in the mammalian genome and we have discovered two, d(delta)-tubulin and e(epsilon)-tubulin. Epsilon tubulin has not been described before in any organism, and its properties suggest a role in centrosome function as well. We will attack four specific aims in the next project period: 1) Determine the subunit composition and structure of the gamma-tubulin complex. 2) Define the interactions among the gamma-tubulin complex proteins, and their role in the gamma-tubulin complex. 3) Characterize the interaction of the gamma-tubulin complex with the microtubule and the centrosome. 4) Characterize the role of epsilon-tubulin in centrosome function.