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

电池极性的控制

• 批准号: 6571155
• 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
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6571155
• 关键词: biological signal transduction; cell cell interaction; cell cycle; cell membrane; cellular polarity; enzyme activity; epithelium; guanine nucleotide binding protein; guanosinetriphosphatases; intermolecular interaction; intracellular transport; membrane activity; neoplastic cell; neurons; protein localization; protein structure function; protein transport; transfection; yeasts

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 膜与细胞骨架之间的相互作用。在许多情况下，这些 相互作用是由细胞外信号引发的，并通过 蛋白质家族还负责控制转录 活性和细胞周期。尽管不完全理解，但 酵母中子细胞的偏光发芽提供了一个惊人的例子 关于GTPa​​ses和相关蛋白的Rho家族如何导致改变 已知和新颖的细胞骨架元素控制细胞形态发生。 考虑到这些回应的基本本质，很有可能 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 暗示确实可能是这种情况。我们建议应用新颖的测定 表征负责启动和维护的机制 哺乳动物细胞的极性，并直接测试 酵母和哺乳动物细胞的极性是通过根本相似的 策略。此外，我们将检查极性之间的关系 和肿瘤发生，因为在 控制细胞极性由已知或可疑的癌基因编码。我们的 具体目的是：i）了解导致初始的事件 上皮细胞，神经元和淋巴细胞的极性发展； ii） 为了表征负责维护独特的机制 在没有细胞细胞接触的情况下，质膜结构域； iii）to 确定基因哺乳动物同源物的细胞内定位 控制酵母中的极化芽，并评估 来自极性似乎有极性的上皮肿瘤的转移细胞 迷路了； iv）表征Rho家族蛋白和 极性的产生或维持中的相关分子 上皮，神经元和淋巴细胞。