NRSA: Interorganellar Phospholipid Transport in Yeast

描述(申请人提供)：本提案侧重于阐明细胞器间脂类转运的分子机制，这一过程对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。虽然对细胞内脂质运输的机制缺乏全面的描述，但在定义酵母模型运输系统的组成部分方面已经取得了重大进展，即磷脂酰丝氨酸从内质网中的合成部位运输到高尔基体，在高尔基体中，磷脂酰丝氨酸在高尔基体中脱羧基，形成磷脂酰乙醇胺。在以前的遗传和生化研究的基础上，我将调查被确定为内质网到高尔基体脂质转运决定因素的蛋白质和脂域的功能，并利用这些研究来测试目前膜间脂转移如何发生的模型。此外，我将研究这一运输途径的调节，并开发新的遗传筛选，以分离在其他细胞内脂质运输过程中存在缺陷的新突变株。

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.