LPT1 encodes a membrane-bound O-acyltransferase involved in the acylation of lysophospholipids in the yeast Saccharomyces cerevisiae
LPT1 encodes a membrane-bound O-acyltransferase involved in the acylation of lysophospholipids in the yeast Saccharomyces cerevisiae
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DOI：
10.1074/jbc.m704509200
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发表时间：
2007-11-23
影响因子：
4.8
通讯作者：
Kumagai, Hidehiko
中科院分区：
文献类型：
--
作者：
Tamaki, Hisanori;Shimada, Atsushi;Kumagai, Hidehiko
磷脂是细胞膜的主要成分，参与一系列细胞过程。磷脂酸（Phosphatidic acid，PA）是磷脂生物合成途径中的关键分子。在酿酒酵母中，SLC 1被鉴定为编码溶血磷脂酸酰基转移酶的基因，该酶催化PA的合成。然而，尽管PA很重要，但SLC 1的破坏不影响细胞活力（Nagiec，M. M.，威尔斯，G. B.，莱斯特河L.，和Dickson，R. C.（1993）J.Biol.Chem.268，22156-22163）。我们最初的目的是确定乙酰辅酶A：溶血血小板活化因子乙酰转移酶（lysoPAF AT）基因在酵母中。筛选一组完整的酵母缺失克隆（4741个纯合二倍体克隆），发现一个单一的突变株，YOR 175 c，在lysoPAF AT活性的缺陷。YOR 175 c被预测为膜结合O-酰基转移酶超家族的成员，我们将其命名为LPT 1。一种定位于内质网的Lpt 1-绿色荧光蛋白融合蛋白。除lysoPAF AT活性外，Lpt 1还催化酰基转移酶活性，并以多种溶血磷脂作为受体，包括溶血磷脂酸、溶血磷脂酰胆碱、溶血磷脂酰乙醇胺、溶血磷脂酰甘油、溶血磷脂酰肌醇和溶血磷脂酰丝氨酸。液相色谱-质谱分析表明，溶血磷脂酰胆碱和溶血磷脂酰乙醇胺积累在德尔塔lpt 1突变株。尽管Delta lpt 1突变株没有显示出其他可检测的缺陷，但Delta lpt 1 Delta slc 1双突变株具有合成致死表型。这些结果表明，与Slc 1一致，Lpt 1在PA生物合成中起着核心作用，这对细胞活力至关重要。
Phospholipids are major components of cellular membranes that participate in a range of cellular processes. Phosphatidic acid (PA) is a key molecule in the phospholipid biosynthetic pathway. In Saccharomyces cerevisiae, SLC1 has been identified as the gene encoding lysophosphatidic acid acyltransferase, which catalyzes PA synthesis. However, despite the importance of PA, disruption of SLC1 does not affect cell viability (Nagiec, M. M., Wells, G. B., Lester, R. L., and Dickson, R. C. (1993) J. Biol. Chem. 268, 22156-22163). We originally aimed to identify the acetyl-CoA: lyso platelet-activating factor acetyltransferase (lysoPAF AT) gene in yeast. Screening of a complete set of yeast deletion clones (4741 homozygous diploid clones) revealed a single mutant strain, YOR175c, with a defect in lysoPAF AT activity. YOR175c has been predicted to be a member of the membrane-bound O-acyltransferase superfamily, and we designated the gene LPT1. An Lpt1-green fluorescent protein fusion protein localized at the endoplasmic reticulum. Other than lysoPAF AT activity, Lpt1 catalyzed acyltransferase activity with a wide variety of lysophospholipids as acceptors, including lysophosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylglycerol, lysophosphatidylinositol, and lysophosphatidylserine. A liquid chromatography-mass spectrometry analysis indicated that lysophosphatidylcholine and lysophosphatidylethanolamine accumulated in the Delta lpt1 mutant strain. Although the Delta lpt1 mutant strain did not show other detectable defects, the Delta lpt1 Delta slc1 double mutant strain had a synthetic lethal phenotype. These results indicate that, in concert with Slc1, Lpt1 plays a central role in PA biosynthesis, which is essential for cell viability.