PER1 is required for GPI-phospholipase A2 activity and involved in lipid remodeling of GPI-anchored proteins
PER1 is required for GPI-phospholipase A2 activity and involved in lipid remodeling of GPI-anchored proteins
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DOI：
10.1091/mbc.e06-08-0715
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发表时间：
2006-12-01
影响因子：
3.3
通讯作者：
Jigami, Yoshifumi
中科院分区：
文献类型：
--
作者：
Fujita, Morihisa;Umemura, Mariko;Jigami, Yoshifumi
糖基磷脂酰肌醇 (GPI) 锚在运输到细胞表面的过程中被重塑。新合成的蛋白质被转移到由二酰基甘油和常规 C16 和 C18 脂肪酸组成的 GPI 锚定上，而成熟 GPI 锚定蛋白质中的脂质部分则被交换为在 sn-2 位上含有 C26:0 脂肪酸的二酰基甘油或酿酒酵母中的神经酰胺。在此，我们报道了 PER1，这是一种编码 GPI 重塑途径所需蛋白质的基因。我们发现 GPI 锚定蛋白不能与 per1 Delta 细胞中的耐去污剂膜结合。此外，突变细胞在从正常磷脂酰肌醇 (PI) 到 GPI 锚点中含有 C26 脂肪酸的 PI 的脂质重塑方面存在缺陷。体外分析表明，PER1 是产生 lyso-GPI 所必需的，这表明 Per1p 拥有或调节 GPI-磷脂酶 A(2) 活性。我们还发现人类 PERLD1 是 PER1 的功能同源物。我们的结果首次证明 PERI 编码 GPI 锚定重塑途径的进化保守成分，强调了 GPI 的脂质重塑与 GPI 锚定蛋白的筏关联之间的密切联系。
Glycosylphoshatidylinositol (GPI) anchors are remodeled during their transport to the cell surface. Newly synthesized proteins are transferred to a GPI anchor, consisting of diacylglycerol with conventional C16 and C18 fatty acids, whereas the lipid moiety in mature GPI-anchored proteins is exchanged to either diacylglycerol containing a C26:0 fatty acid in the sn-2 position or ceramide in Saccharomyces cerevisiae. Here, we report on PER1, a gene encoding a protein that is required for the GPI remodeling pathway. We found that GPI-anchored proteins could not associate with the detergent-resistant membranes in per1 Delta cells. In addition, the mutant cells had a defect in the lipid remodeling from normal phosphatidylinositol (PI) to a C26 fatty acid-containing PI in the GPI anchor. In vitro analysis showed that PER1 is required for the production of lyso-GPI, suggesting that Per1p possesses or regulates the GPI-phospholipase A(2) activity. We also found that human PERLD1 is a functional homologue of PER1. Our results demonstrate for the first time that PERI encodes an evolutionary conserved component of the GPI anchor remodeling pathway, highlighting the close connection between the lipid remodeling of GPI and raft association of GPI-anchored proteins.