REGULATED PROTEIN DELIVERY TO THE PLASMA MEMBRANE

调节蛋白质向质膜的输送

• 批准号: 6151199
• 负责人: Chris Alan Kaiser
• 金额: $ 28.1万
• 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 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6151199
• 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控制递送 将蛋白质运输到质膜，使细胞能够 吸收小分子来响应细胞外信号。 博士 凯泽的研究小组提出了一种结合基因和 对酵母S.酿酒厂提供基本的 对整合膜的调节递送机制的洞察 蛋白质到质膜。 凯泽博士实验室的最新工作 已经表明，在酵母中传递的一般氨基酸通透酶 （Gap 1）对质膜的反应是对细胞中氮源的反应。 生长培养基 Gap 1的细胞定位调节需要 在反式高尔基体中Gap 1被装载到运输囊泡中的位置 定向于质膜或液泡。 在这 应用，凯泽博士建议阐明Gap 1的机制 在trans-Golgi中排序。 这些研究将包括发展 用于形成含Gap 1的细胞的体内和体外测定 囊泡，以及基因产物的鉴定和表征 控制Gap 1 p排序。 蛋白质向质膜的调节递送是 人体细胞生理学 例如，GLUT 4葡萄糖 转运蛋白被递送到脂肪和肌肉细胞的质膜 在胰岛素的反应，和缺陷，在这种管制贩运， 尽管这是非胰岛素依赖型糖尿病的根本原因。 小 已知控制GLUT 4或其他基因定位的机制， 调节人类的膜蛋白。 然而，在S.啤酒厂 将有可能充分利用一个发达的基因 生物体，以揭示基因和蛋白质负责调节 在高尔基体中进行分类。 从S.酿酒厂应该提供 哺乳动物的基因有着相似的功能， 用于诊断哺乳动物中功能障碍性分选的新方法， 细胞，并提供新的机会，选择性地改变血浆 细胞膜的组成。