PGAP2 is essential for correct processing and stable expression of GPI-anchored proteins
PGAP2 is essential for correct processing and stable expression of GPI-anchored proteins
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DOI：
10.1091/mbc.e05-11-1005
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发表时间：
2006-03-01
影响因子：
3.3
通讯作者：
Maeda, Y
中科院分区：
文献类型：
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作者：
Tashima, Y;Taguchi, R;Maeda, Y
糖基磷脂酰肌醇锚定蛋白（GPI-AP）在内质网中的生物合成已被广泛研究，而GPI-AP从内质网运输到细胞表面的分子事件知之甚少。在这里，我们建立了新的突变细胞系，其GPI-AP的表面表达大大降低，尽管在ER中GPI-AP的正常生物合成。我们确定了一个负责这种缺陷的基因，命名为PGAP 2（GPI后附着蛋白2），它编码高尔基体/ER驻留膜蛋白。GPI-AP的低表面表达是由于它们分泌到培养基中。GPI-AP在突变细胞中通过两个反应步骤被修饰/切割。首先，GPI锚在离开trans-Golgi网络之前转化为溶血-GPI。其次，溶血-GPI-AP在运输到质膜后被磷脂酶D切割。因此，PGAP 2缺陷导致对磷脂酶D敏感的溶血GPI-AP转运至细胞表面。这些结果表明PGAP 2参与GPI-AP在细胞表面稳定表达所需的加工。
Biosynthesis of glycosylphosphatidylinositol-anchored proteins (GPI-APs) in the ER has been extensively studied, whereas the molecular events during the transport of GPI-APs from the ER to the cell surface are poorly understood. Here, we established new mutant cell lines whose surface expressions of GPI-APs were greatly decreased despite normal biosynthesis of GPI-APs in the ER. We identified a gene responsible for this defect, designated PGAP2 (for Post-GPI-Attachment to Proteins 2), which encoded a Golgi/ER-resident membrane protein. The low surface expression of GPI-APs was due to their secretion into the culture medium. GPI-APs were modified/cleaved by two reaction steps in the mutant cells. First, the GPI anchor was converted to lyso-GPI before exiting the trans-Golgi network. Second, lyso-GPI-APs were cleaved by a phospholipase D after transport to the plasma membrane. Therefore, PGAP2 deficiency caused transport to the cell surface of lyso-GPI-APs that were sensitive to a phospholipase D. These results demonstrate that PGAP2 is involved in the processing of GPI-APs required for their stable expression at the cell surface.