Publications

• Lysophospholipid acyltransferases and arachidonate recycling in human neutrophils.

  Gijon M.A., Riekhof W.R., Zarini S., Murphy R.C., Voelker D.R.

  The cycle of deacylation and reacylation of phospholipids plays a critical role in regulating availability of arachidonic acid for eicosanoid production. The major yeast lysophospholipid acyltransferase, Ale1p, is related to mammalian membrane-bound O-acyltransferase (MBOAT) proteins. We expressed ... >> More

  The cycle of deacylation and reacylation of phospholipids plays a critical role in regulating availability of arachidonic acid for eicosanoid production. The major yeast lysophospholipid acyltransferase, Ale1p, is related to mammalian membrane-bound O-acyltransferase (MBOAT) proteins. We expressed four human MBOATs in yeast strains lacking Ale1p and studied their acyl-CoA and lysophospholipid specificities using novel mass spectrometry-based enzyme assays. MBOAT1 is a lysophosphatidylserine (lyso-PS) acyltransferase with preference for oleoyl-CoA. MBOAT2 also prefers oleoyl-CoA, using lysophosphatidic acid and lysophosphatidylethanolamine as acyl acceptors. MBOAT5 prefers lysophosphatidylcholine and lyso-PS to incorporate linoleoyl and arachidonoyl chains. MBOAT7 is a lysophosphatidylinositol acyltransferase with remarkable specificity for arachidonoyl-CoA. MBOAT5 and MBOAT7 are particularly susceptible to inhibition by thimerosal. Human neutrophils express mRNA for these four enzymes, and neutrophil microsomes incorporate arachidonoyl chains into phosphatidylinositol, phosphatidylcholine, PS, and phosphatidylethanolamine in a thimerosal-sensitive manner. These results strongly implicate MBOAT5 and MBOAT7 in arachidonate recycling, thus regulating free arachidonic acid levels and leukotriene synthesis in neutrophils. << Less

  J. Biol. Chem. 283:30235-30245(2008) [PubMed] [EuropePMC]

  This publication is cited by 26 other entries.

• Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity.

  Hishikawa D., Shindou H., Kobayashi S., Nakanishi H., Taguchi R., Shimizu T.

  All organisms consist of cells that are enclosed by a cell membrane containing bipolar lipids and proteins. Glycerophospholipids are important not only as structural and functional components of cellular membrane but also as precursors of various lipid mediators. Polyunsaturated fatty acids compri ... >> More

  All organisms consist of cells that are enclosed by a cell membrane containing bipolar lipids and proteins. Glycerophospholipids are important not only as structural and functional components of cellular membrane but also as precursors of various lipid mediators. Polyunsaturated fatty acids comprising arachidonic acid or eicosapentaenoic acid are located at sn-2 position, but not at sn-1 position of glycerophospholipids in an asymmetrical manner. In addition to the asymmetry, the membrane diversity is important for membrane fluidity and curvature. To explain the asymmetrical distribution of fatty acids, the rapid turnover of sn-2 position was proposed in 1958 by Lands [Lands WE (1958) Metabolism of glycerolipides: A comparison of lecithin and triglyceride synthesis. J Biol Chem 231:883-888]. However, the molecular mechanisms and biological significance of the asymmetry remained unknown. Here, we describe a putative enzyme superfamily consisting mainly of three gene families, which catalyzes the transfer of acyl-CoAs to lysophospholipids to produce different classes of phospholipids. Among them, we characterized three important enzymes with different substrate specificities and tissue distributions; one, termed lysophosphatidylcholine acyltransferase-3 (a mammalian homologue of Drosophila nessy critical for embryogenesis), prefers arachidonoyl-CoA, and the other two enzymes incorporate oleoyl-CoAs to lysophosphatidylethanolamine and lysophosphatidylserine. Thus, we propose that the membrane diversity is produced by the concerted and overlapped reactions with multiple enzymes that recognize both the polar head group of glycerophospholipids and various acyl-CoAs. Our findings constitute a critical milestone for our understanding about how membrane diversity and asymmetry are established and their biological significance. << Less

  Proc. Natl. Acad. Sci. U.S.A. 105:2830-2835(2008) [PubMed] [EuropePMC]

  This publication is cited by 23 other entries.

• Drosophila lysophospholipid acyltransferases are specifically required for germ cell development.

  Steinhauer J., Gijon M.A., Riekhof W.R., Voelker D.R., Murphy R.C., Treisman J.E.

  Enzymes of the membrane-bound O-acyltransferase (MBOAT) family add fatty acyl chains to a diverse range of protein and lipid substrates. A chromosomal translocation disrupting human MBOAT1 results in a novel syndrome characterized by male sterility and brachydactyly. We have found that the Drosoph ... >> More

  Enzymes of the membrane-bound O-acyltransferase (MBOAT) family add fatty acyl chains to a diverse range of protein and lipid substrates. A chromosomal translocation disrupting human MBOAT1 results in a novel syndrome characterized by male sterility and brachydactyly. We have found that the Drosophila homologues of MBOAT1, Oysgedart (Oys), Nessy (Nes), and Farjavit (Frj), are lysophospholipid acyltransferases. When expressed in yeast, these MBOATs esterify specific lysophospholipids preferentially with unsaturated fatty acids. Generating null mutations for each gene allowed us to identify redundant functions for Oys and Nes in two distinct aspects of Drosophila germ cell development. Embryos lacking both oys and nes show defects in the ability of germ cells to migrate into the mesoderm, a process guided by lipid signals. In addition, oys nes double mutant adult males are sterile due to specific defects in spermatid individualization. oys nes mutant testes, as well as single, double, and triple mutant whole adult animals, show an increase in the saturated fatty acid content of several phospholipid species. Our findings suggest that lysophospholipid acyltransferase activity is essential for germline development and could provide a mechanistic explanation for the etiology of the human MBOAT1 mutation. << Less

  Mol. Biol. Cell 20:5224-5235(2009) [PubMed] [EuropePMC]

  This publication is cited by 16 other entries.