HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 42, 30845-30855, October 19, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/42/30845    most recent M702719200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Benghezal, M. Articles by Conzelmann, A. Search for Related Content PubMed PubMed Citation Articles by Benghezal, M. Articles by Conzelmann, A. Social Bookmarking                      What's this?

SLC1 and SLC4 Encode Partially Redundant Acyl-Coenzyme A 1-Acylglycerol-3-phosphate O-Acyltransferases of Budding Yeast^*

Mohammed Benghezal¹, Carole Roubaty, Vijayanath Veepuri², Jens Knudsen, and Andreas Conzelmann³

From the Department of Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland and the University of Southern Denmark, DK-5230 Odense M, Denmark

Phosphatidic acid is the intermediate, from which all glycerophospholipids are synthesized. In yeast, it is generated from lysophosphatidic acid, which is acylated by Slc1p, an sn-2-specific, acyl-coenzyme A-dependent 1-acylglycerol-3-phosphate O-acyltransferase. Deletion of SLC1 is not lethal and does not eliminate all microsomal 1-acylglycerol-3-phosphate O-acyltransferase activity, suggesting that an additional enzyme may exist. Here we show that SLC4 (Yor175c), a gene of hitherto unknown function, encodes a second 1-acyl-sn-glycerol-3-phosphate acyltransferase. SLC4 harbors a membrane-bound O-acyltransferase motif and down-regulation of SLC4 strongly reduces 1-acyl-sn-glycerol-3-phosphate acyltransferase activity in microsomes from slc1 cells. The simultaneous deletion of SLC1 and SLC4 is lethal. Mass spectrometric analysis of lipids from slc1 and slc4 cells demonstrates that in vivo Slc1p and Slc4p generate almost the same glycerophospholipid profile. Microsomes from slc1 and slc4 cells incubated with [¹⁴C]oleoyl-coenzyme A in the absence of lysophosphatidic acid and without CTP still incorporate the label into glycerophospholipids, indicating that Slc1p and Slc4p can also use endogenous lysoglycerophospholipids as substrates. However, the lipid profiles generated by microsomes from slc1 and slc4 cells are different, and this suggests that Slc1p and Slc4p have a different substrate specificity or have access to different lyso-glycerophospholipid substrates because of a different subcellular location. Indeed, affinity-purified Slc1p displays Mg²⁺-dependent acyltransferase activity not only toward lysophosphatidic acid but also lyso forms of phosphatidylserine and phosphatidylinositol. Thus, Slc1p and Slc4p may not only be active as 1-acylglycerol-3-phosphate O-acyltransferases but also be involved in fatty acid exchange at the sn-2-position of mature glycerophospholipids.

Received for publication, March 29, 2007 , and in revised form, August 3, 2007.

^* This work was supported by Swiss National Science Foundation Grant 31-67188.01. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S4.

¹ Present address: Helicobacter Research Laboratory, Microbiology M502, University of Western Australia, QEII Medical Centre, Nedlands 6009, Western Australia.

² Present address: H.No: 11-9/5, New Gaddiannaram, Hyderabad 500060, India.

³ To whom all correspondence should be addressed: Division of Biochemistry, Chemin du Musée 5, CH-1700 Fribourg, Switzerland. Tel.: 41-26-300-8630; Fax: 41-26-300-9735; E-mail: andreas.conzelmann{at}unifr.ch.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Jain, X. Zhang, P. J. Khandelwal, A. J. Saunders, B. S. Cummings, and P. Oelkers Characterization of human lysophospholipid acyltransferase 3 J. Lipid Res., August 1, 2009; 50(8): 1563 - 1570. [Abstract] [Full Text] [PDF]

				K. Yuki, H. Shindou, D. Hishikawa, and T. Shimizu Characterization of mouse lysophosphatidic acid acyltransferase 3: an enzyme with dual functions in the testis J. Lipid Res., May 1, 2009; 50(5): 860 - 869. [Abstract] [Full Text] [PDF]

				C. S. Ejsing, J. L. Sampaio, V. Surendranath, E. Duchoslav, K. Ekroos, R. W. Klemm, K. Simons, and A. Shevchenko From the Cover: Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry PNAS, February 17, 2009; 106(7): 2136 - 2141. [Abstract] [Full Text] [PDF]

				H. Shindou and T. Shimizu Acyl-CoA:Lysophospholipid Acyltransferases J. Biol. Chem., January 2, 2009; 284(1): 1 - 5. [Abstract] [Full Text] [PDF]

				M. A. Gijon, W. R. Riekhof, S. Zarini, R. C. Murphy, and D. R. Voelker Lysophospholipid Acyltransferases and Arachidonate Recycling in Human Neutrophils J. Biol. Chem., October 31, 2008; 283(44): 30235 - 30245. [Abstract] [Full Text] [PDF]

				K. Stalberg, A. C. Neal, H. Ronne, and U. Stahl Identification of a novel GPCAT activity and a new pathway for phosphatidylcholine biosynthesis in S. cerevisiae J. Lipid Res., August 1, 2008; 49(8): 1794 - 1806. [Abstract] [Full Text] [PDF]

				S. Matsuda, T. Inoue, H.-C. Lee, N. Kono, F. Tanaka, K. Gengyo-Ando, S. Mitani, and H. Arai Member of the membrane-bound O-acyltransferase (MBOAT) family encodes a lysophospholipid acyltransferase with broad substrate specificity. Genes Cells, August 1, 2008; 13(8): 879 - 888. [Abstract] [Full Text] [PDF]

				A. K. Ghosh, G. Ramakrishnan, and R. Rajasekharan YLR099C (ICT1) Encodes a Soluble Acyl-CoA-dependent Lysophosphatidic Acid Acyltransferase Responsible for Enhanced Phospholipid Synthesis on Organic Solvent Stress in Saccharomyces cerevisiae J. Biol. Chem., April 11, 2008; 283(15): 9768 - 9775. [Abstract] [Full Text] [PDF]

				Y. Zhao, Y.-Q. Chen, T. M. Bonacci, D. S. Bredt, S. Li, W. R. Bensch, D. E. Moller, M. Kowala, R. J. Konrad, and G. Cao Identification and Characterization of a Major Liver Lysophosphatidylcholine Acyltransferase J. Biol. Chem., March 28, 2008; 283(13): 8258 - 8265. [Abstract] [Full Text] [PDF]

				H.-C. Lee, T. Inoue, R. Imae, N. Kono, S. Shirae, S. Matsuda, K. Gengyo-Ando, S. Mitani, and H. Arai Caenorhabditis elegans mboa-7, a Member of the MBOAT Family, Is Required for Selective Incorporation of Polyunsaturated Fatty Acids into Phosphatidylinositol Mol. Biol. Cell, March 1, 2008; 19(3): 1174 - 1184. [Abstract] [Full Text] [PDF]

				D. Hishikawa, H. Shindou, S. Kobayashi, H. Nakanishi, R. Taguchi, and T. Shimizu Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity PNAS, February 26, 2008; 105(8): 2830 - 2835. [Abstract] [Full Text] [PDF]

				W. R. Riekhof, J. Wu, M. A. Gijon, S. Zarini, R. C. Murphy, and D. R. Voelker Lysophosphatidylcholine Metabolism in Saccharomyces cerevisiae: THE ROLE OF P-TYPE ATPases IN TRANSPORT AND A BROAD SPECIFICITY ACYLTRANSFERASE IN ACYLATION J. Biol. Chem., December 21, 2007; 282(51): 36853 - 36861. [Abstract] [Full Text] [PDF]

				S. Jain, N. Stanford, N. Bhagwat, B. Seiler, M. Costanzo, C. Boone, and P. Oelkers Identification of a Novel Lysophospholipid Acyltransferase in Saccharomyces cerevisiae J. Biol. Chem., October 19, 2007; 282(42): 30562 - 30569. [Abstract] [Full Text] [PDF]