Mechanisms of Nuclear Positioning and Microtubule Organization

核定位和微管组织机制

• 批准号: 7347593
• 负责人: Fred Chang
• 金额: $ 27.17万
• 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/7347593
• 关键词: Address; Area; Binding; Biological Assay; Bundling; Cancer Biology; Cancer Etiology; Cell Cycle; Cell Nucleus; Cell division; Cells; Centrifugation; Centrosome; Complex; Cytokinesis; Cytoskeleton; Defect; Development; Epithelial; Eukaryotic Cell; Fission Yeast; Interphase; Life; Link; Localized; Location; Malignant Neoplasms; Mammalian Cell; Mediating; Membrane Proteins; Microtubule Bundle; Microtubule-Organizing Center; Microtubules; Mitotic spindle; Modeling; Molecular; Molecular Chaperones; Muscle Cells; Nuclear; Nuclear Envelope; Numbers; Positioning Attribute; Process; Proteins; Regulation; Research Personnel; Role; Site; Structure; Tertiary Protein Structure; Testing; Work; anticancer research; base; cell type; cellular imaging; env Gene Products; gamma Tubulin; genetic analysis; insight; novel; particle; spindle pole body

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(MTOCs)的调节有助于微管细胞骨架在细胞周期和发育过程中的重组。裂殖酵母裂殖酵母庞贝细胞使用三种类型的MTOCs在细胞周期中构建不同的微管结构。间期，微管束由核膜上的多个间期微管组织中心(IMTOCs)组成。IMTOCs是核定位所必需的，可能含有参与微管成核、捆绑和附着到核膜上的蛋白质。IMTOC的建立发生在胞质分裂过程中，与位于细胞分裂部位的赤道MTOC(EMTOC)的解体同时发生。在这里，我们将确定协调eMTOC的分解和iMTOC的形成的机制。我们的具体目标是：1)确定J结构域蛋白rsp1p和MTOC蛋白coi1p在调节Emtoc拆解中的作用。2)确定含有MTOC组分的运动颗粒(卫星)的功能。我们将测试一个模型，即卫星将MTOC组件从正在分解的eMTOC运送到核包膜，在那里它们有助于iMTOC的形成。3)鉴定核膜蛋白，将iMTOC和间期MT束连接到核膜外膜，用于核定位。这项工作将为许多细胞类型的微管的调节提供洞察力，例如上皮细胞和肌肉细胞。由于中心体缺陷在癌症中普遍存在，MTOC的调节现在是癌症研究的一个重要领域。