REGULATED PROTEIN DELIVERY TO THE PLASMA MEMBRANE

调节蛋白质向质膜的输送

• 批准号: 6351233
• 负责人: Chris Alan Kaiser
• 金额: $ 28.71万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6351233
• 关键词: Golgi apparatus; Saccharomyces cerevisiae; bioassay; cell membrane; fungal genetics; gene mutation; genetic regulation; growth /development; intracellular transport; laboratory rabbit; membrane proteins; nitrogen; permease; polymerase chain reaction; protein sequence; protein transport; vesicle /vacuole

An important aspect of cell regulation is the controlled delivery of transport proteins to the plasma membrane, allowing the cells capacity to take up small molecules to respond to extracellular signals. Dr. Kaiser's research group proposes a combination of genetic and biochemical experiments in the yeast S. cerevisiae to give fundamental insight into the mechanism of regulated delivery of integral membrane proteins to the plasma membrane. Recent work in Dr. Kaiser's laboratory has shown that in yeast delivery of the general amino acid permease (Gap1) to the plasma membrane responds to the nitrogen source in the growth medium. The regulation of the cellular location of Gap1 takes place in the trans-Golgi where Gap1 is loaded into transport vesicles directed either to the plasma membrane or to the vacuole. In this application, Dr. Kaiser proposes to elucidate the mechanism of Gap1 sorting in the trans-Golgi. These studies will include development of in vivo and in vitro assays for the formation of Gap1-containing vesicles, and the identification and characterization of gene products that control Gap1p sorting. The regulated delivery of proteins to the plasma membrane is key to human cell physiology. For example, the GLUT4 glucose transporter is delivered to the plasma membrane of fat and muscle cells in response to insulin, and defects in this regulated trafficking are though to be a root cause of non-insulin- dependent diabetes. Little is known of the mechanisms that control the location of GLUT4 or other regulated membrane proteins in humans. However, in S. cerevisiae it will be possible to apply the full power of a well developed genetic organism to uncover the genes and proteins responsible for regulated sorting in the Golgi. The genes from S. cerevisiae should give access to the mammalian genes that perform similar functions, opening the way to new methods for the diagnosis of dysfunctional sorting in mammalian cells and providing new opportunities to selectively alter the plasma membrane composition of cells.

细胞调节的一个重要方面是受控的交付 将蛋白质传输到质膜，使细胞容量 占用小分子以对细胞外信号做出反应。 博士 Kaiser的研究小组提出了遗传和 酵母菌S.酿酒酵母中的生化实验可提供基本 深入了解整体膜的调节递送机制 蛋白质到质膜。 Kaiser博士实验室的最新工作 已经表明，在一般氨基酸渗透酶的酵母菌递送中 （GAP1）到质膜对氮源的反应 生长培养基。 GAP1的细胞位置的调节 将GAP1加载到传输囊泡中 针对质膜或液泡。 在这个 Kaiser博士建议阐明GAP1的机制 在反式高尔基体中排序。 这些研究将包括开发 体内和体外测定，用于形成含GAP1的 囊泡，以及基因产物的鉴定和表征 控制GAP1P排序。 蛋白质向质膜的调节递送是 人类细胞生理。 例如，Glut4葡萄​​糖 转运蛋白被输送到脂肪和肌肉细胞的质膜 响应胰岛素和这种受监管的贩运的缺陷是 虽然是非胰岛素依赖性糖尿病的根本原因。 小的 已知控制GLUT4或其他位置的机制 调节人类的膜蛋白。 但是，在酿酒酵母中 将有可能运用良好发达的遗传的全部力量 有机体发现负责调节的基因和蛋白质 在高尔基体中排序。 酿酒酵母的基因应提供 对执行类似功能的哺乳动物基因开放 到诊断哺乳动物功能失调分选的新方法 细胞并提供新的机会来选择性改变等离子体 细胞的膜组成。