NRSA: Interorganellar Phospholipid Transport in Yeast

NRSA：酵母中的细胞器间磷脂运输

• 批准号: 7289868
• 负责人: Wayne Riekhof
• 金额: $ 2.52万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7289868
• 关键词: 1-Phosphatidylinositol 4-Kinase; Binding Proteins; Biochemical; Biochemical Genetics; Biological Assay; Carboxy-Lyases; Cells; Complex; Defect; Development; Dissection; Endoplasmic Reticulum; Ethanolamines; Eukaryotic Cell; Event; Figs - dietary; Genetic Screening; Golgi Apparatus; Growth; In Vitro; Lipid Binding; Lipids; Mediating; Membrane; Metabolism; Mitochondria; Modeling; Molecular; National Research Service Awards; Pathway interactions; Phosphatidylethanolamine; Phosphatidylinositols; Phosphatidylserines; Phospholipids; Process; Proteins; Regulation; Screening procedure; Site; Source; Supplementation; System; Testing; Transport Process; Work; Yeasts; ethanolamine; lipid transport; membrane biogenesis; mutant; novel; phosphatidylethanolamine; protein function; reconstitution; research study; tool; trafficking; uptake

DESCRIPTION (provided by applicant): This proposal focuses on elucidation of the molecular mechanisms of interorganellar lipid transport, a process that is crucial for the membrane biogenesis and growth of all eukaryotic cells, but which has traditionally been regarded as a difficult problem. While a thorough mechanistic description for intracellular lipid transport is lacking, significant progress has been made in defining components of a model transport system in yeast, namely, transport of phosphatidylserine from its site of synthesis in the endoplasmic reticulum to the Golgi compartment, where it is decarboxylated to form phosphatidylethanolamine. Building upon previous genetic and biochemical studies, I will investigate the function of the proteins and lipid domains that have been identified as determinants of ER to Golgi lipid transport, and use these studies to test current models of how intermembrane lipid transfer takes place. Additionally, I will study the regulation of this transport pathway, and develop new genetic screens to isolate novel mutants defective in components of other intracellular lipid transport processes.

描述（由申请人提供）：该提案侧重于阐明细胞间脂质转运的分子机制，该过程对于所有真核细胞的膜生物发生和生长至关重要，但传统上被认为是一个难题。虽然缺乏对细胞内脂质转运的彻底机制描述，但在定义酵母模型转运系统的组成部分方面已经取得了重大进展，即将磷脂酰丝氨酸从内质网中的合成位点转运到高尔基体区室，在高尔基体区室中脱羧形成磷脂酰乙醇胺。在之前的遗传和生化研究的基础上，我将研究已被确定为内质网至高尔基体脂质转运决定因素的蛋白质和脂质结构域的功能，并利用这些研究来测试膜间脂质转移如何发生的当前模型。此外，我将研究这种运输途径的调节，并开发新的遗传筛选，以分离其他细胞内脂质运输过程的组成部分有缺陷的新突变体。