Microtubule Organization and Nuclear Positioning

描述（由申请人提供）：微管是细胞骨架元件，负责细胞的空间组织。它们执行关键的细胞过程，如染色体分离、细胞极化和细胞迁移。MT +末端的动态行为——它们的生长、收缩、靶向和附着——由一系列MT相关因素调节。本文以分裂酵母裂糖酵母（Schizosaccharomyces pombe）为模型生物，研究了调节MT细胞骨架的分子机制。我们的研究重点是阐明调控MT生长和收缩转变的机制，即MT救援和灾难。我们的目标是：1)表征CLASP，一种稳定有丝分裂纺锤体和间期MT束内MT的候选MT拯救因子；2)确定MT突变事件发生在细胞尖端特定皮质部位的原因；3)探讨肌动蛋白在细胞核中的可能作用，重点研究其在有丝分裂过程中对染色体分离的影响。

DESCRIPTION (provided by applicant): Microtubules are cytoskeletal elements responsible for the spatial organization of cells. They carry out critical cellular processes such as chromosome segregation, cell polarization and cell migration. The dynamic behaviors of MT plus ends - their growth, shrinkage, targeting and attachment -- are modulated by a bevy of MT-associated factors. Here, we study the molecular mechanisms that regulate the MT cytoskeleton, using the fission yeast Schizosaccharomyces pombe as a model organism. Our studies focus on elucidating the mechanisms that regulate the transitions between MT growth and shrinkage, namely MT rescue and catastrophe. Our aims are: 1) to characterize CLASP, a candidate MT rescue factor that stabilizes MTs within the mitotic spindle and interphase MT bundles; 2) to determine why MT catastrophe events occur at specific cortical sites at cell tips; 3) to investigate possible roles of actin in the nucleus, focusing on its effect on chromosome segregation during mitosis. PUBLIC HEALTH RELEVANCE: Microtubules are dynamic filaments responsible for cell division and determination of cell shape and function. In this proposal we will determine how the growth and shrinkage of microtubules are regulated. These studies will provide greater understanding of how mitotic spindles work and will be relevant for human diseases such as cancer.