NRSA: Interorganellar Phospholipid Transport in Yeast

描述（由申请人提供）：本提案的重点是阐明细胞器间脂质转运的分子机制，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。虽然缺乏对细胞内脂质运输的彻底机制描述，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的合成位点运输到高尔基室，在那里它被脱羧形成磷脂酰乙醇胺。在先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到高尔基脂转运的决定因素的蛋白质和脂质结构域的功能，并使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，我将研究这一转运途径的调控，并开发新的遗传筛选，以分离在其他细胞内脂质转运过程组分中存在缺陷的新突变体。

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.