Regulation of Cell Polarity and Exocytosis

细胞极性和胞吐作用的调节

• 批准号: 6743685
• 负责人: PATRICK J BRENNWALD
• 金额: $ 32.74万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6743685
• 关键词: SDS polyacrylamide gel electrophoresis; Saccharomyces cerevisiae; biological transport; cell membrane; cellular polarity; enzyme activity; enzyme biosynthesis; exocytosis; gene interaction; guanine nucleotide binding protein; guanosinetriphosphatases; polymerase chain reaction; protein biosynthesis; protein structure function; yeast two hybrid system

DESCRIPTION (provided by applicant): Delivery of proteins to the proper place on the cell surface is important for a large number of cell biological processes, including the development of cellular asymmetry and polarity. The delivery of ceil surface components is accomplished primarily by the delivery of transport vesicles that fuse with a specific region of the ptasma membrane. We are examining plasma membrane targeting events in the yeast, Saccharomyces cerevisiae, in order to take advantage of the genetic and cell biological tools available in this organism. SNARE proteins are thought to play a central role in the targeting and/or fusion of transport vesicles with the plasma membrane, and we have identified and extensively characterized a set of SNARE proteins, which are required for ceil surface transport in yeast. Our genetic and biochemical analysis of these proteins has led us to the identification of a new regulatory pathway involving the Rho GTPases Cdc42 and Rho3, as well as a novel Sec9 binding protein, called Sro7, related to the Drosophila tumor suppressor lethal giant larvae. Recent work from our lab suggests that Cdc42 function in exocytosis is restricted to very early in bud emergence while Rho3 appears to function in this regard throughout the cell cycle. This suggests that this pathway may be central to the overall coordination of the polarity of the actin cytoskeleton with the polarity of cell surface delivery. Evidence from a mammalian epithelial cell culture model suggests that Sro7/Lgl function in exocytosis is conserved in higher eukaryotic cells. These studies will have important implications in both understanding the function of Rho GTPases in exocytosis as well as m unraveling a novel mechanism for regulation of t-SNARE function at the plasma membrane. This regulation may represent a key mechanism by which eukaryotic cells regulate and coordinate the polarity of the actin cytoskeleton with the polarized delivery of protein and lipid to the cell surface. Finally studies from other systems suggest that loss of function in this pathway is tied to the loss of polarity in epithelial cells, which may play a key role in the tumorigenic transformation of epithelial cells--the most common source of cancer in humans.

描述（由申请人提供）：将蛋白质递送到细胞表面的适当位置对于大量细胞生物过程，包括细胞不对称和极性的发展很重要。 CEIL表面成分的递送主要是通过与甲状腺膜特定区域融合的传输囊泡来完成的。我们正在研究酿酒酵母酵母中的质膜靶向事件，以利用这种生物体可用的遗传和细胞生物学工具。 SNARE蛋白被认为在传输囊泡与质膜的靶向和/或融合中起着核心作用，我们已经确定并广泛地表征了一组SNARE蛋白，这是酵母中天花表面运输所必需的。我们对这些蛋白质的遗传和生化分析使我们能够鉴定涉及Rho GTPases Cdc42和Rho3的新调节途径，以及一种与果蝇抑制果蝇抑制剂lethal巨型巨型幼虫有关的新型SEC9结合蛋白，称为SRO7。我们实验室的最新工作表明，胞吞作用中的Cdc42功能仅限于芽出现的早期，而Rho3在整个细胞周期中似乎在这方面起作用。这表明该途径可能是肌动蛋白细胞骨架极性与细胞表面递送极性的总体配位。来自哺乳动物上皮细胞培养模型的证据表明，在较高的真核细胞中，胞吞作用中的SRO7/LGL功能是保守的。这些研究将对理解Rho GTPases在胞吞作用中的功能以及M揭示调节质膜T-Snare功能的新机制的功能具有重要意义。该调节可能代表着一种关键机制，真核细胞通过该机制调节并协调肌动蛋白细胞骨架的极性与蛋白质和脂质向细胞表面的极化递送。最后，来自其他系统的研究表明，该途径中的功能丧失与上皮细胞中极性的丧失有关，这可能在上皮细胞的肿瘤性转化中起关键作用，这是人类最常见的癌症来源。