Changes in molecular species profiles of glycosylphosphatidylinositol anchor precursors in early stages of biosynthesis
Changes in molecular species profiles of glycosylphosphatidylinositol anchor precursors in early stages of biosynthesis
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DOI：
10.1194/jlr.m700095-jlr200
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发表时间：
2007-07-01
影响因子：
6.5
通讯作者：
Taguchi, Ryo
中科院分区：
文献类型：
--
作者：
Houjou, Toshiaki;Hayakawa, Jun;Taguchi, Ryo
糖基磷脂酰肌醇（GPI）锚是翻译后修饰的主要脂化作用。GPI锚前体由内源性磷脂酰肌醇（PI）生物合成并附着于内质网中的蛋白质。内源性PI的特征在于在sn-2位上二酰基种类占优势并且存在多不饱和脂肪酰基链，例如18：0-20：4。与此相反，哺乳动物糖基磷脂酰肌醇锚定蛋白（GPI-AP）的功能是占主导地位的烷基/酰基PI物种和饱和脂肪酰基链的存在下，在sn-2位置，后者是一致的与脂筏协会。最近的研究表明，在sn-2的饱和脂肪酰基链是通过GPI-AP中发生的脂肪酸重构引入的。为了深入了解前一个功能，我们分析了几种不同的GPI前体的分子物种来自各种哺乳动物突变细胞系。在这里，我们表明，PI物种的配置文件大大改变了前体葡糖胺（GlcN）-酰基-PI，变得非常相似的GPI-AP脂肪酸重塑之前。它们具有烷基（或烯基）/酰基型，其中不饱和酰基链是主要的PI物种。因此，成熟GPI-AP的PI部分的特定特征，烷基（或烯基）/酰基类型种类相对于二酰基类型的优势，在GlcN-酰基-PI阶段建立。
Glycosylphosphatidylinositol (GPI) anchor is a major lipidation in posttranslational modification. GPI anchor precursors are biosynthesized from endogenous phosphatidylinositols (PIs) and attached to proteins in the endoplasmic reticulum. Endogenous PIs are characterized by domination of diacyl species and the presence of polyunsaturated fatty acyl chain, such as 18:0-20:4, at the sn-2 position. In contrast, the features of mammalian glycosylphosphatidylinositol-anchored proteins (GPI-APs) are domination of alkyl/acyl PI species and the presence of saturated fatty acyl chains at the sn-2 position, the latter being consistent with association with lipid rafts. Recent studies showed that saturated fatty acyl chain at sn-2 is introduced by fatty acid remodeling that occurs in GPI-APs. To gain insight into the former feature, we analyzed the molecular species of several different GPI precursors derived from various mammalian mutant cell lines. Here, we show that the PI species profile greatly changed in the precursor glucosamine (GlcN)-acyl-PI and became very similar to that of GPI-APs before fatty acid remodeling. They had alkyl (or alkenyl)/ acyl types with unsaturated acyl chain as the major PI species. Therefore, a specific feature of the PI moieties of mature GPI-APs, domination of alkyl (or alkenyl)/acyl type species over diacyl types, is established at the stage of GlcN-acyl-PI.