Assembly and Placement of the Cell Division Ring

细胞分裂环的组装和放置

• 批准号: 6573010
• 负责人: Fred Chang
• 金额: $ 35.41万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6573010
• 关键词: Escherichia coli; Schizosaccharomyces pombe; actin binding protein; actins; cell cycle; cell migration; cellular polarity; chimeric proteins; confocal scanning microscopy; fluorescence microscopy; fungal genetics; fungal proteins; gel filtration chromatography; gene expression; gene interaction; green fluorescent proteins; immunoprecipitation; intermolecular interaction; intracellular transport; microtubules; protein binding; protein biosynthesis; protein kinase; protein structure function; protein transport; western blottings; yeast two hybrid system

DESCRIPTION (provided by applicant): Interactions between microtubules and actin are critical for proper spatial organization in cells. During cytokinesis in animal cells, microtubules of the mitotic spindle position the cell division plane. Similar interactions between microtubules and actin also appear to regulate cell polarity and cell migration. The molecular mechanisms for these interactions are unknown. We study spatial regulation in the fission yeast Schizosaccharomyces pombe, a rod-shaped cell that grows from the cell tips and divides in the middle. The goal of this work is to determine how the sites of cell division and cell growth are positioned in the cell. Our preliminary results suggest that cell polarity and cytokinesis are regulated by particles that move to the cell tips or to the cell middle, dock at the plasma membrane, and then function to induce assembly of actin structures (actin cables for cell growth or the contractile actin ring for cytokinesis). In this grant, we propose to study these key motile particles: how do they move to specific locations in the cell, what are their molecular compositions and what are their functions? Our specific aims are: 1) to determine how plus-ends of microtubules deposit a particle containing the cell polarity factor tea1p at the cell tips; 2) to determine how tea1p functions at the cell tip to recruit a "polarisome" protein complex that assembles actin cables; 3) to determine how microtubules and actin target a motile particle containing the cytokinesis factor cdc12p to the future cell division site at the middle of the cell. These studies will elucidate a molecular mechanism for how microtubules regulate the spatial distribution of actin. As many of the proteins in these processes are conserved, this work will be directly relevant to general mechanisms of cell polarity and cell division that will be important for understanding development and human diseases such as cancer.

描述（由申请人提供）：微管和肌动蛋白之间的相互作用对于细胞中的适当空间组织至关重要。在动物细胞的胞质分裂过程中，有丝分裂纺锤体的微管定位细胞分裂平面。微管和肌动蛋白之间类似的相互作用似乎也调节细胞极性和细胞迁移。这些相互作用的分子机制尚不清楚。我们研究了裂殖酵母裂殖酵母的空间调控，裂殖酵母是一种杆状细胞，从细胞尖端生长，在中间分裂。这项工作的目标是确定细胞分裂和细胞生长的位点如何在细胞中定位。我们的初步研究结果表明，细胞极性和胞质分裂是由移动到细胞尖端或细胞中间，停靠在质膜上的颗粒调节的，然后起作用以诱导肌动蛋白结构（用于细胞生长的肌动蛋白电缆或用于胞质分裂的收缩肌动蛋白环）的组装。在这项资助中，我们建议研究这些关键的运动粒子：它们如何移动到细胞中的特定位置，它们的分子组成是什么，它们的功能是什么？我们的具体目标是：1）确定微管的正端如何将含有细胞极性因子tea 1 p的颗粒沉积在细胞尖端; 2）确定tea 1 p如何在细胞尖端起作用以募集组装肌动蛋白电缆的“极性体”蛋白复合物; 3）确定微管和肌动蛋白如何将含有胞质分裂因子cdc 12 p的运动颗粒靶向细胞中部的未来细胞分裂位点。这些研究将阐明微管如何调节肌动蛋白空间分布的分子机制。由于这些过程中的许多蛋白质是保守的，这项工作将与细胞极性和细胞分裂的一般机制直接相关，这对于理解发育和人类疾病（如癌症）非常重要。