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: 6520370
• 负责人: MARGARET T FULLER
• 金额: $ 18.78万
• 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/6520370
• 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）：胞质分裂是一个基本的过程， 都是分裂的动物细胞然而，调节和调解的机制 F-肌动蛋白收缩环的局部组装，其稳定的附着 到细胞皮层，其协调拆卸是未知的。我们有 确定了29个新基因的突变，这些基因在不同的特定阶段是必需的。 果蝇雄性减数分裂期间的胞质分裂。这批变种人展示了 这是一个无与伦比的机会来阐明介导 调节动物细胞的胞质分裂。F-actin收缩蛋白的组装 戒指需要詹姆斯邦德和至少八个其他基因。弗罗多的职能是 保持收缩性肌动球蛋白环和苯胺醛之间的连接， 细胞皮层胞质分裂需要FTV、FSCO、FUN、ONR和BNS 和极化细胞生长在精子细胞伸长，表明一个共同的 潜在机制为了研究他们的阶段和行动方式，我们将 确定基因是否是组装或定位其他基因所必需的， 收缩环蛋白，中间纺锤体成分，和关键的肌动蛋白调节 分子如CDC 42或Arp 2/3复合物亚基。为了调查 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-肌动蛋白装配， 拆卸或重组或定位的关键肌动蛋白相关的 蛋白质在胞质分裂和延长精子细胞的尖端。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， 中心纺锤体，或精子细胞鞭毛，测试它们的定位如何依赖于 已知胞质分裂基因的野生型功能，并测试是否 它们可以结合苯胺、隔膜、微管或肌动蛋白，或成束、切断或成帽 微丝，或成核的F-肌动蛋白组装在体外。