Drs2p Function in Clathrin-coated Vesicle Budding

Drs2p 在网格蛋白包被的囊泡出芽中的功能

• 批准号: 6655530
• 负责人: TODD R GRAHAM
• 金额: $ 24.16万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6655530
• 关键词: ADP ribosylation; G protein; Saccharomyces cerevisiae; cell component structure /function; cell free system; clathrin; electron microscopy; fungal genetics; fungal proteins; hydrogen potassium exchanging ATPase; intracellular transport; membrane lipids; membrane reconstitution /synthesis; membrane transport proteins; molecular site; phospholipids; posttranslational modifications; protein localization; protein structure function; site directed mutagenesis; technology /technique development; vesicle /vacuole

DESCRIPTION (APPLICANT'S ABSTRACT): A striking feature of eukaryotic cells, from yeast to human, is their compartmental organization into membrane-bound organelles, each with a unique composition and function. The long-term goal of this research project is to understand how the Goigi complex, a multi-compartment organelle, performs its essential role in the transport, modification and sorting of proteins in the secretory pathway. Towards this goal, the function of ADP-ribosylation factor (ARF) in vesicle-mediated transport from the Golgi complex is being examined. ARF appears to regulate the budding of both COPI- and clathrin-coated vesicles from the Golgi complex. The proposed studies stem from recent discoveries implicating a role for Drs2p, an integral membrane P-type ATPase and potential lipid translocase (or flippase), specifically in the ARF-dependent budding of clathrin coated vesicles. The yeast Saccharomyces cerevisiae will be used for this work because of the fundamental similarity of the secretory pathway in all eukaryotic cells coupled with the powerful genetic and molecular approaches available with this organism make it an ideal model system. The specific goals of this research project are to determine if Drs2p is required for recruiting ARF and clathrin to Golgi membranes, thus indicating a direct role for Drs2p in clathrin coated vesicle budding. The proposed lipid flippase activity of Drs2p will be tested as will the potential overlap in function between Drs2p and four Drs2p-related proteins encoded within the yeast genome. There are profound implications to human health that can be derived from this study. Both Drs2p and clathrin are required for the normal function of the Golgi complex in the transport and processing of many proteins. In addition, lipid flippases related to Drs2p are thought to restrict phosphatidylserine (PS) to the inner leaflet of 'the plasma membrane. Loss of this asymmetric distribution of PS in blood cells stimulates clot formation and in apoptotic cells allows for recognition and phagocytosis by macrophages.

描述（申请人摘要）：真核细胞的一个显著特征，