MOLECULAR STUDIES OF EUKARYOTIC CELL SURFACE GROWTH

真核细胞表面生长的分子研究

• 批准号: 6385369
• 负责人: RANDY W. SCHEKMAN
• 金额: $ 17.43万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6385369
• 关键词: SDS polyacrylamide gel electrophoresis; Saccharomyces cerevisiae; beta fructofuranosidase; cell cycle; cell membrane; chitin; clathrin; density gradient ultracentrifugation; developmental genetics; electron microscopy; enzyme activity; eukaryote; gene expression; genetic regulation; immunoelectron microscopy; immunoprecipitation; laboratory rabbit; membrane proteins; molecular cloning; protein transport; secretory protein; vesicle /vacuole; western blottings

Protein secretion is a fundamentally conserved process that provides a mechanism for cells to create stable intracellular compartments such as the ER, Golgi, lysosome, and plasma membrane, and to communicate with external cells and tissues. A genetic, molecular cloning, and biochemical analysis of this process in Saccharomyces cerevisiae has uncovered genes and mechanisms that are shared among all eukaryotes. This proposal develops a new line of investigation concerning the mechanism of transport vesicle formation from the trans Golgi cisterna and of the pathway of vesicle traffic to the cytokinesis furrow which forms early in the yeast cell cycle. Evidence has emerged to suggest multiple paths of transport vesicle formation from the trans Golgi, at least one of which involves vesicular traffic through the endosome en route to the cell surface. Genetic and cell fractionation analysis is proposed to relate secretion to the known pathway of sorting to the endosome, to discover new genes involved in budding from the Golgi, and to use biochemical analysis to clarify the role of clathrin in one of the budding pathways. Certain membrane enzymes are transported through the endosome to the nascent division septum where they participate in forming a cell wall structure that marks the site of yeast bud emergence (the chitin ring) early in the cell cycle. The pathway and regulation of transport of these enzymes from the endosome to the nascent septeum will be examined to understand the mechanism and cell cycle control of this essential process. The study of these processes in yeast cells has illuminated fundamental aspects of cell and organelle growth that are shared by human cells. Furthermore, the application of this knowledge has allowed biotechnology and pharmaceutical companies to harness yeast cells to express and secrete commercial quantities of important hormones, blood proteins, growth factors, and viral antigens.

蛋白质分泌是一个从根本上保守的过程，可提供 细胞创建稳定细胞内室的机制，例如 ER，Golgi，溶酶体和质膜，并与 外细胞和组织。 遗传，分子克隆和 酿酒酵母中此过程的生化分析具有 在所有真核生物中共享的发现的基因和机制。 该提案开发了有关 来自反式高尔基硫酸盐的传输囊泡形成机理 以及囊泡流量到细胞因子沟的途径 在酵母细胞周期的早期形式。 有证据表明有多种运输囊泡的路径 来自反式高尔基体的形成，其中至少涉及囊泡 通过内体的交通在通往细胞表面的途中。 遗传和 提出了细胞分馏分析将分泌与已知的分泌有关 分类到内体的途径，发现涉及的新基因 从高尔基人发芽，并使用生化分析来澄清 网格蛋白在萌芽途径之一中的作用。 某些膜酶通过内体运输到 新生的隔膜，他们参与形成细胞壁 标记酵母芽出现位置的结构（几丁质环） 在细胞周期的早期。 运输的途径和调节 将检查这些从内体到新生隔膜的酶 了解该必需的机制和细胞周期控制 过程。 对酵母细胞中这些过程的研究已经照亮了基本 人类细胞共享细胞和细胞器生长方面。 此外，这种知识的应用允许生物技术 和制药公司利用酵母细胞表达和 分泌重要的激素，血蛋白的商业量， 生长因子和病毒抗原。