GPI Glycan Remodeling by PGAP5 Regulates Transport of GPI-Anchored Proteins from the ER to the Golgi
GPI Glycan Remodeling by PGAP5 Regulates Transport of GPI-Anchored Proteins from the ER to the Golgi
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DOI：
10.1016/j.cell.2009.08.040
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发表时间：
2009-10-16
期刊：
影响因子：
64.5
通讯作者：
Kinoshita, Taroh
中科院分区：
文献类型：
--
作者：
Fujita, Morihisa;Maeda, Yusuke;Kinoshita, Taroh
许多真核蛋白通过糖基磷脂酰肌醇(GPI)锚点附着在细胞表面。GPI锚定蛋白(GPI-AP)是如何从内质网(ER)运输到细胞表面的，目前还知之甚少，但GPI部分被认为是分选和运输的信号。在这里，我们建立了突变细胞，这些突变细胞在将GPI-AP从内质网运输到高尔基体的过程中存在选择性缺陷。我们确定了一个相关基因，命名为PGAP5(后GPI-附着到蛋白5)。PGAP5属于含双金属的磷酸酯酶家族，催化GPI-AP上的糖链重塑。PGAP5的催化活性是GPI-AP有效退出内质网的先决条件。我们的研究结果表明，GPI多糖作为内质网退出信号，提示PGAP5介导的糖链重塑在早期分泌途径中调节GPI-AP的运输。
Many eukaryotic proteins are attached to the cell surface via glycosylphosphatidylinositol (GPI) anchors. How GPI-anchored proteins (GPI-APs) are trafficked from the endoplasmic reticulum (ER) to the cell surface is poorly understood, but the GPI moiety has been postulated to function as a signal for sorting and transport. Here, we established mutant cells that were selectively defective in transport of GPI-APs from the ER to the Golgi. We identified a responsible gene, designated PGAP5 (post-GPI-attachment to proteins 5). PGAP5 belongs to a dimetal-containing phosphoesterase family and catalyzed the remodeling of the glycan moiety on GPI-APs. PGAP5 catalytic activity is a prerequisite for the efficient exit of GPI-APs from the ER. Our data demonstrate that GPI glycan acts as an ER-exit signal and suggest that glycan remodeling mediated by PGAP5 regulates GPI-AP transport in the early secretory pathway.