Caenorhabditis elegans mboa-7, a member of the MBOAT family, is required for selective incorporation of polyunsaturated fatty acids into phosphatidylinositol
Caenorhabditis elegans mboa-7, a member of the MBOAT family, is required for selective incorporation of polyunsaturated fatty acids into phosphatidylinositol
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DOI：
10.1091/mbc.e07-09-0893
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发表时间：
2008-03-01
影响因子：
3.3
通讯作者：
Arai, Hiroyuki
中科院分区：
文献类型：
--
作者：
Lee, Hyeon-Cheol;Inoue, Takao;Arai, Hiroyuki
磷脂酰肌醇（PI）是膜磷脂的一种成分，它以多磷酸肌苷的形式作为信号分子和室特异性定位信号。花生四烯酸（AA）是哺乳动物PI sn-2位的主要脂肪酸。LysoPI酰基转移酶（LPIAT）被认为可以催化含aa的PI的形成；然而，编码这种酶的基因尚未被确定。在这项研究中，我们建立了一个筛选系统，以鉴定在秀丽隐杆线虫中使用外源多不饱和脂肪酸（PUFAs）所需的基因。在秀丽隐杆线虫中，二十碳五烯酸（eicosapentaenoic acid， EPA）代替AA是PI的主要脂肪酸。我们发现了一个未被描述的基因，我们将其命名为mboa-7，它是PUFAs整合到PI中所必需的。在mboa-7突变体中，外源性PUFA掺入活体蠕虫的PI和微粒体中的LPIAT活性大大降低。此外，表达重组MBOA-7及其人类同源物的转基因蠕虫的膜组分显示出显著增加的LPIAT活性。mboa-7编码膜结合o -酰基转移酶家族的一个成员，表明mboa-7是LPIAT。最后，mboa-7突变体在PI中的EPA水平显著降低，并且表现出幼虫阻滞和产卵缺陷。
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.