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Vol. 19, Issue 3, 1174-1184, March 2008

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Caenorhabditis elegans mboa-7, a Member of the MBOAT Family, Is Required for Selective Incorporation of Polyunsaturated Fatty Acids into Phosphatidylinositol

Hyeon-Cheol Lee^*, Takao Inoue^*,, Rieko Imae^*, Nozomu Kono^*, Shinichiro Shirae^*, Shinji Matsuda^*, Keiko Gengyo-Ando^,, Shohei Mitani^,, and Hiroyuki Arai^*,

*Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan; Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo 162-8666, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan

Submitted September 12, 2007; Revised November 16, 2007; Accepted December 12, 2007
Monitoring Editor: Reid Gilmore

Phosphatidylinositol (PI) is a component of membrane phospholipids, and it functions both as a signaling molecule and as a compartment-specific localization signal in the form of polyphosphoinositides. Arachidonic acid (AA) is the predominant fatty acid in the sn-2 position of PI in mammals. LysoPI acyltransferase (LPIAT) is thought to catalyze formation of AA-containing PI; however, the gene that encodes this enzyme has not yet been identified. In this study, we established a screening system to identify genes required for use of exogenous polyunsaturated fatty acids (PUFAs) in Caenorhabditis elegans. In C. elegans, eicosapentaenoic acid (EPA) instead of AA is the predominant fatty acid in PI. We showed that an uncharacterized gene, which we named mboa-7, is required for incorporation of PUFAs into PI. Incorporation of exogenous PUFA into PI of the living worms and LPIAT activity in the microsomes were greatly reduced in mboa-7 mutants. Furthermore, the membrane fractions of transgenic worms expressing recombinant MBOA-7 and its human homologue exhibited remarkably increased LPIAT activity. mboa-7 encodes a member of the membrane-bound O-acyltransferase family, suggesting that mboa-7 is LPIAT. Finally, mboa-7 mutants had significantly lower EPA levels in PI, and they exhibited larval arrest and egg-laying defects.

Address correspondence to: Hiroyuki Arai (harai{at}mol.f.u-tokyo.ac.jp) or Takao Inoue (takao{at}mol.f.u-tokyo.ac.jp)

Abbreviations used: AA, arachidonic acid; CoA, coenzyme A; EPA, eicosapentaenoic acid; GC, gas chromatography; GFP, green fluorescent protein; NGM, nematode growth medium; PA, phosphatidic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; PS, phosphatidylserine; PUFA, polyunsaturated fatty acid; siRNA, small interfering RNA; WT, wild-type; X:Yn-Z, fatty acid chain of X carbon atoms and Y methylene-interrupted cis bonds (Z indicates the position of the terminal double bond relative to the methyl end of the molecules).