Caenorhabditis elegans mboa-7, a member of the MBOAT family, is required for selective incorporation of polyunsaturated fatty acids into phosphatidylinositol.
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.
Lee
Hyeon-Cheol
HC
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Inoue
Takao
T
Imae
Rieko
R
Kono
Nozomu
N
Shirae
Shinichiro
S
Matsuda
Shinji
S
Gengyo-Ando
Keiko
K
Mitani
Shohei
S
Arai
Hiroyuki
H
D000217:Acyltransferases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D017238:Genes, Helminth; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010716:Phosphatidylinositols / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D001095:Arachidonic Acids; D029742:Caenorhabditis elegans Proteins; D005231:Fatty Acids, Unsaturated; D010716:Phosphatidylinositols; D011994:Recombinant Proteins; D000217:Acyltransferases; C021522:lysophosphatidylinositol acyltransferase