GENETIC DISSECTION OF CYTOKINESIS AND CELL MORPHOGENESIS

描述(申请人的描述)：胞质分裂是 所有动物细胞都在分裂。然而，调节和调解的机制 F-肌动蛋白收缩环的局部组装及其稳定附着 到细胞皮质，以及它的协调分解尚不清楚。我们有 确定了29个新基因的突变，这些基因是在不同的特定阶段所需的 果蝇雄性减数分裂过程中的胞质分裂。这个变种人收藏展示了 一个无与伦比的机会来阐明 并调节动物细胞的胞质分裂。F-肌动蛋白收缩的组装 RING需要詹姆斯邦德和至少八个其他基因。FRODO函数用于 保持收缩的acto-myosin环和苯丙氨酸之间的联系 细胞皮质。FTVS、FSCO、FUN、ONR和BNS都是胞质分裂所必需的 以及在精子细胞伸长过程中极化细胞的生长，这表明 潜在的机制。为了调查他们的阶段和行动模式，我们将 确定这些基因是否需要组装或定位其他 收缩环蛋白、中纺锤体组件和关键肌动蛋白调节 分子如Cdc42或Arp2/3复合亚单位。调查共同之处 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， 关键肌动蛋白相关基因的拆解、重组或本地化 胞质分裂和伸长精子细胞顶端的蛋白质。至 阐明胞质分裂的分子机制，我们将克隆选定的基因， 确定他们的蛋白质产物是否是收缩环的成分， 中央纺锤体，或精子细胞鞭毛，测试它们的定位如何依赖于 已知的胞质分裂基因的野生型功能及其相互作用，并测试 它们可以结合芳香素、隔膜、微管或肌动蛋白，或捆绑、切断或封口。 微丝，或在体外有核的F-肌动蛋白组装。

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.