Mechanisms of Nuclear Positioning and Microtubule Organization

核定位和微管组织机制

• 批准号: 7011213
• 负责人: Fred Chang
• 金额: $ 26.21万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7011213
• 关键词: Schizosaccharomyces pombe; cell cycle; confocal scanning microscopy; gene targeting; green fluorescent proteins; immunoprecipitation; microtubules; nuclear membrane; protein localization; protein protein interaction; tubulin

DESCRIPTION (provided by applicant): Regulation of microtubule organizing centers (MTOCs) contributes to the reorganization of the microtubule cytoskeleton during the cell cycle and in development. Fission yeast Schizosaccharomyces pombe cells use three types of MTOCs for building different microtubule structures through the cell cycle. During interphase, microtubule bundles are organized by multiple interphase microtubule organizing centers (iMTOCs) on the nuclear envelope. iMTOCs are required for nuclear positioning and may contain proteins involved in microtubule nucleation, bundling and attachment to the nuclear envelope. Establishment of iMTOCs occurs during cytokinesis, concurrent with the disassembly of the equatorial MTOC (eMTOC) located at the cell division site. Here, we will determine mechanisms that orchestrate the breakdown of the eMTOC and the formation of iMTOCs. Our specific aims are: 1) to determine the roles of a J-domain protein rsp1p and an MTOC protein coi1p in regulation of Emtoc disassembly. 2) To determine the function of motile particles (satellites) containing MTOC components. We will test a model that satellites transport MTOC components from the disassemblying eMTOC to the nuclear envelope, where they contribute to iMTOC formation. 3) To identify nuclear envelope proteins that attaches iMTOCs and interphase MT bundles to the outer nuclear envelope for nuclear positioning. This work will provide insights into the regulation of microtubules of many cell types such as epithelial and muscle cells. As centrosomal defects are prevalent in cancer, MTOC regulation is now an important area in cancer research.

描述（由申请人提供）：微管组织中心（MTOC）的调节有助于在细胞周期和发育过程中重组微管细胞骨架。裂变酵母菌型酸糖液细胞使用三种类型的MTOC在整个细胞周期中构建不同的微管结构。在相间期间，微管束由核包膜上的多个相间微管组织中心（IMTOC）组织。 IMTOC是核定位所必需的，可能包含参与微管成核，捆绑和附着在核包膜上的蛋白质。 IMTOC的建立发生在细胞因子期间，同时与位于细胞分裂部位的赤道MTOC（EMTOC）拆卸。在这里，我们将确定策划EMTOC分解和IMTOC形成的机制。我们的具体目的是：1）确定J-域蛋白RSP1P和MTOC蛋白COI1P在EMTOC拆卸调节中的作用。 2）确定含有MTOC分量的运动颗粒（卫星）的功能。我们将测试一个模型，卫星将MTOC组件从拆卸的EMTOC传输到核包膜，并在其中促进IMTOC形成。 3）确定将IMTOC和相间MT束附加到外核包膜上的核包膜蛋白进行核定位。这项工作将提供有关许多细胞类型（例如上皮细胞和肌肉细胞）微管调节的见解。由于中心缺陷在癌症中很普遍，因此MTOC调节现在是癌症研究中的重要领域。