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. ? ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F05-J (20))
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Rodewald, Richard D
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National Jewish Health
United States
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Kannan, Muthukumar; Riekhof, Wayne R; Voelker, Dennis R (2015) Transport of phosphatidylserine from the endoplasmic reticulum to the site of phosphatidylserine decarboxylase2 in yeast. Traffic 16:123-34
Riekhof, Wayne R; Naik, Surabhi; Bertrand, Helmut et al. (2014) Phosphate starvation in fungi induces the replacement of phosphatidylcholine with the phosphorus-free betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine. Eukaryot Cell 13:749-57
Riekhof, Wayne R; Wu, Wen-I; Jones, Jennifer L et al. (2014) An assembly of proteins and lipid domains regulates transport of phosphatidylserine to phosphatidylserine decarboxylase 2 in Saccharomyces cerevisiae. J Biol Chem 289:5809-19
Brechbuhl, Heather M; Gould, Neal; Kachadourian, Remy et al. (2010) Glutathione transport is a unique function of the ATP-binding cassette protein ABCG2. J Biol Chem 285:16582-7
Riekhof, Wayne R; Voelker, Dennis R (2009) The yeast plasma membrane P4-ATPases are major transporters for lysophospholipids. Biochim Biophys Acta 1791:620-7
Steinhauer, Josefa; Gijón, Miguel A; Riekhof, Wayne R et al. (2009) Drosophila lysophospholipid acyltransferases are specifically required for germ cell development. Mol Biol Cell 20:5224-35
Gijon, Miguel A; Riekhof, Wayne R; Zarini, Simona et al. (2008) Lysophospholipid acyltransferases and arachidonate recycling in human neutrophils. J Biol Chem 283:30235-45
Riekhof, Wayne R; Wu, James; Gijon, Miguel A et al. (2007) Lysophosphatidylcholine metabolism in Saccharomyces cerevisiae: the role of P-type ATPases in transport and a broad specificity acyltransferase in acylation. J Biol Chem 282:36853-61
Riekhof, Wayne R; Wu, James; Jones, Jennifer L et al. (2007) Identification and characterization of the major lysophosphatidylethanolamine acyltransferase in Saccharomyces cerevisiae. J Biol Chem 282:28344-52
Riekhof, Wayne R; Voelker, Dennis R (2006) Uptake and utilization of lyso-phosphatidylethanolamine by Saccharomyces cerevisiae. J Biol Chem 281:36588-96