GUP1 of Saccharomyces cerevisiae encodes an O-acyltransferase involved in remodeling of the GPI anchor
GUP1 of Saccharomyces cerevisiae encodes an O-acyltransferase involved in remodeling of the GPI anchor
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DOI：
10.1091/mbc.e06-02-0104
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发表时间：
2006-06-01
影响因子：
3.3
通讯作者：
Conzelmann, Andreas
中科院分区：
文献类型：
--
作者：
Bosson, Regine;Jaquenoud, Malika;Conzelmann, Andreas
酿酒酵母成熟的糖基磷脂酰肌醇(GPI)锚定蛋白的锚定含有神经酰胺或二酰甘油，SN2位含有C26：0脂肪酸。在内质网中，添加到新合成的蛋白质中的初级GPI类脂由二酰甘油以及常规的C16和C18脂肪酸组成。在这里，我们证明了GUP1对于合成含C26：0的二酰基甘油锚是必不可少的。Gup1p是一种具有多个跨膜结构域的内质网膜蛋白，具有膜结合O-酰基转移酶(MBOAT)的基序。Gup1 Delta细胞产生正常数量的GPI蛋白，但大多数成熟的GPI锚点含有溶血磷脂酰肌醇，其他细胞含有磷脂酰肌醇和常规的C16和C18脂肪酸。正常神经酰胺与锚杆的结合也受到干扰。结果，GPI蛋白Gas1p从内质网到高尔基体的运输缓慢，成熟的Gas1p从质膜丢失到培养液中。Gup1 Delta细胞细胞壁脆弱，两极芽位选择存在缺陷。GUP1的功能依赖于MBOAT基序的活性部位组氨酸。GUP1在真菌和原生动物中高度保守，GUP1的Delta型部分被烟曲霉和克鲁兹锥虫的GUP1同源物纠正。
The anchors of mature glycosylphosphatidylinositol (GPI)-anchored proteins of Saccharomyces cerevisiae contain either ceramide or diacylglycerol with a C26:0 fatty acid in the sn2 position. The primary GPI lipid added to newly synthesized proteins in the ER consists of diacylglycerol with conventional C16 and C18 fatty acids. Here we show that GUP1 is essential for the synthesis of the C26:0-containing diacylglycerol anchors. Gup1p is an ER membrane protein with multiple membrane-spanning domains harboring a motif that is characteristic of membrane-bound O-acyl-transferases (MBOAT). Gup1 Delta cells make normal amounts of GPI proteins but most mature GPI anchors contain lyso-phosphatidylinositol, and others possess phosphatidylinositol with conventional C16 and C18 fatty acids. The incorporation of the normal ceramides into the anchors is also disturbed. As a consequence, the ER-to-Golgi transport of the GPI protein Gas1p is slow, and mature Gas1p is lost from the plasma membrane into the medium. Gup1 Delta cells have fragile cell walls and a defect in bipolar bud site selection. GUP1 function depends on the active site histidine of the MBOAT motif. GUP1 is highly conserved among fungi and protozoa and the gup1 Delta phenotype is partially corrected by GUP1 homologues of Aspergillus fumigatus and Trypanosoma cruzi.