Gamma tubulin ring complex in microtubule nucleation

描述(由申请人提供)：长期目标是了解中心体如何在动物细胞中组装和发挥作用。中心体是微管的主要成核和组织中心，参与间期细胞质和有丝分裂纺锤体的组织。在有丝分裂中，在细胞周期的S阶段复制的两个中心体有效地组成了一个两极纺锤体。最近的研究表明，错误调控的中心体复制会导致单极或多极纺锤体和染色体的错误分离，将癌症的形成与中心体功能障碍联系起来。因此，了解中心体的结构和功能关系到人类的健康。这项资助试图通过研究中心体上发现的一种大型蛋白质复合体--伽马微管蛋白环复合体(GammaTuRC)来研究中心体介导的微管成核和中心体组装的机制。GammaTuRC是中心体上重要的微管核因子，是中心体组装所必需的。在这个授予期间，我们希望了解1)GammaTuRC是如何由多个亚基组装而成的，2)GammaTuRC是如何在微管成核和组织中发挥作用的，3)GammaTuRC是如何被招募到中心体参与微管成核和中心体组装的。

DESCRIPTION (provided by applicant): The long-term goal is to understand how the centrosome assembles and functions in animal cells. The centrosome is the major microtubule nucleating and organizing center that participates in organizing interphase cytoplasm and mitotic spindle poles. In mitosis, a bipolar spindle is organized efficiently from two centrosomes duplicated during S phase of the cell cycle. Recent studies suggested that mis-regulated centrosome duplication lead to mono- or multi-polar spindles and chromosome mis-segregation, linking cancer formation to centrosome dysfunction. Therefore, understanding the structure and function of the centrosome is relevant to human health. This grant seeks to study the mechanism of centrosome-mediated microtubule nucleation and centrosome assembly via studying a large protein complex, the gamma-tubulin ring complex (gammaTuRC) found at the centrosome. gammaTuRC is an important microtubule nucleator at the centrosome and it is required for centrosome assembly. In this granting period, we hope to understand 1) how gammaTuRC is assembled from multiple subunits, 2) how gammaTuRC functions in microtubule nucleation and organization, 3) how gammaTuRC is recruited to the centrosome to participate in microtubule nucleation and centrosome assembly.