CONTROL OF CELL POLARITY & PLASMA MEMBRANE FUNCTION BY RHO FAMILY GTPASE

电池极性的控制

基本信息

批准号：
6437378
负责人：
IRA S MELLMAN
金额：
$ 19.72万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-03-07 至 2001-12-31
项目状态：
已结题

项目摘要

Crucial aspects of cellular organization and function are determined by interactions between membranes and the cytoskeleton. In many cases, these interactions are initiated by extracellular signals and transduced by families of proteins also responsible for controlling transcriptional activity and the cell cycle. Although incompletely understood, the polarized budding of daughter cells in yeast provides a striking example of how rho family of GTPases and related proteins lead to alterations of known and novel cytoskeletal elements to control cellular morphogenesis. Given the fundamental natures of these responses, it is highly likely that a similar cascade of events is responsible for controlling morphogenesis and polarity in mammalian cells. Recent evidence provides provocative hints that this may indeed be the case. We propose to apply novel assays to characterize the mechanisms responsible for initiating and maintaining polarity in mammalian cells, and to directly test the possibility that polarity in yeast and mammalian cells is mediated by fundamentally similar strategies. In addition, we will examine the relationship between polarity and tumorigenesis, since proteins which are strong candidates in controlling cell polarity are encoded by known or suspected oncogenes. Our Specific Aims are: i) to understand the events leading to the initial development of polarity in epithelial cells, neurons and lymphocytes; ii) To characterize the mechanisms responsible for the maintenance of distinct plasma membrane domains in the absence of cell-cell contact; iii) To determine the intracellular localization of mammalian homologs of genes that control polarized budding in yeast, and evaluate alterations in metastatic cells from epithelial tumors where polarity appears to have been lost; and iv) To characterize the function of rho family proteins and related molecules in the generation or maintenance of polarity in epithelia, neurons, and lymphocytes.

细胞组织和功能的关键方面由以下因素决定膜和细胞骨架之间的相互作用。在许多情况下，这些相互作用由细胞外信号引发并通过蛋白质家族也负责控制转录活动和细胞周期。虽然不完全理解，酵母子细胞的极化出芽提供了一个引人注目的例子 GTPases 的 rho 家族和相关蛋白如何导致控制细胞形态发生的已知和新颖的细胞骨架元件。鉴于这些反应的基本性质，很可能类似的级联事件负责控制形态发生和哺乳动物细胞的极性。最近的证据提供了挑衅性的暗示情况可能确实如此。我们建议应用新的检测方法描述负责启动和维持的机制哺乳动物细胞的极性，并直接测试可能性酵母和哺乳动物细胞中的极性是由基本相似的介导的策略。此外，我们还将研究极性之间的关系和肿瘤发生，因为蛋白质是强有力的候选者控制细胞极性是由已知或可疑的癌基因编码的。我们的具体目标是： i) 了解导致最初的事件上皮细胞、神经元和淋巴细胞极性的发展；二）描述负责维持不同的机制的特征在没有细胞与细胞接触的情况下质膜结构域； iii) 至确定哺乳动物基因同源物的细胞内定位控制酵母中的极化出芽，并评估来自上皮肿瘤的转移细胞，其极性似乎具有迷路了； iv) 表征 rho 家族蛋白的功能和极性产生或维持的相关分子上皮细胞、神经元和淋巴细胞。