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. ? ? ?
