GENETIC DISSECTION OF CYTOKINESIS AND CELL MORPHOGENESIS

细胞分裂和细胞形态发生的基因解剖

• 批准号: 6228426
• 负责人: MARGARET T FULLER
• 金额: $ 17.87万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6228426
• 关键词: Drosophilidae; actins; cytogenetics; gene mutation; intracellular transport; meiosis; microtubules; molecular cloning; protein localization; sperm analysis

DESCRIPTION (applicant's description): Cytokinesis is a fundamental process in all dividing animal cells. However, the mechanisms that regulate and mediate the localized assembly of the F-actin contractile ring, its stable attachment to the cell cortex, and its coordinated disassembly are not known. We have identified mutations in 29 new genes required at different specific stages of cytokinesis during male meiosis in Drosophila. This mutant collection presents an unparalleled opportunity to elucidate the molecular mechanisms that mediate and regulate cytokinesis in animal cells. Assembly of the F-actin contractile ring requires james bond and at least eight other genes. frodo functions to maintain linkage between the constricting acto-myosin ring and anillin at the cell cortex. ftvs, fsco, fun, onr, and bns are required for both cytokinesis and polarized cell outgrowth during spermatid elongation, suggesting a common underlying mechanism. To investigate their stage and mode of action we will determine if the genes are required for assembly or localization of other contractile ring proteins, mid-spindle components, and key actin regulatory molecules such as CDC42 or Arp2/3 complex subunits. To investigate the common mechanism required for cytokinesis and flagellar elongation, we will determine if the fws, fsco, etc. mutations similarly affect F-actin assembly, disassembly, or reorganization or the localization of key actin-associated proteins during cytokinesis and at the tip of elongating spermatids. To elucidate molecular mechanisms of cytokinesis, we will clone selected genes, determine if their protein products are components of the contractile ring, central spindle, or spermatid flagella, test how their localization depends on wild type function of known cytokinesis genes and each other, and test whether they can bind anillin, septins, microtubules or actin, or bundle, sever, or cap microfilaments, or nucleate F-actin assembly in vitro.

描述（申请人的描述）：细胞分裂是细胞分裂的一个基本过程。 所有正在分裂的动物细胞。然而，调节和介导的机制 F-肌动蛋白收缩环的局部组装及其稳定附着 细胞皮质的作用及其协调分解尚不清楚。我们有 确定了不同特定阶段所需的 29 个新基因的突变 果蝇雄性减数分裂期间的胞质分裂。这个突变体系列呈现 阐明介导的分子机制的无与伦比的机会 并调节动物细胞的胞质分裂。 F-肌动蛋白收缩体的组装 戒指需要詹姆斯·邦德和至少八个其他基因。 frodo 的功能是 维持收缩肌动球蛋白环和苯胺之间的联系 细胞皮质。 ftvs、fsco、fun、onr 和 bns 是两种胞质分裂所必需的 和精子细胞伸长过程中极化细胞的生长，表明一个常见的 底层机制。为了调查他们的阶段和行动方式，我们将 确定这些基因是否是组装或定位其他基因所必需的 收缩环蛋白、中纺锤体成分和关键肌动蛋白调节 CDC42 或 Arp2/3 复合体亚基等分子。为调查常见的 胞质分裂和鞭毛伸长所需的机制，我们将确定 如果 fws、fsco 等突变类似地影响 F-肌动蛋白组装， 关键肌动蛋白相关蛋白的拆卸、重组或定位 胞质分裂期间和伸长精子细胞尖端的蛋白质。到 阐明胞质分裂的分子机制，我们将克隆选定的基因， 确定它们的蛋白质产物是否是收缩环的组成部分， 中央纺锤体或精子鞭毛，测试它们的定位如何取决于 已知胞质分裂基因和彼此的野生型功能，并测试是否 它们可以结合苯胺、脓蛋白、微管或肌动蛋白，或束、切断或帽 微丝，或体外有核 F-肌动蛋白组装。