Fujita Morihisa, Maeda Yusuke, Ra Moonjin, Yamaguchi Yoshiki, Taguchi Ryo, Kinoshita Taroh
Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Cell. 2009 Oct 16;139(2):352-65. doi: 10.1016/j.cell.2009.08.040.
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.
许多真核生物蛋白质通过糖基磷脂酰肌醇（GPI）锚定在细胞表面。GPI锚定蛋白（GPI-APs）如何从内质网（ER）转运到细胞表面尚不清楚，但GPI部分被认为作为分选和运输的信号。在这里，我们建立了在GPI-APs从ER到高尔基体的运输中选择性缺陷的突变细胞。我们鉴定出一个负责的基因，命名为PGAP5（蛋白GPI附着后5）。PGAP5属于含二金属的磷酸酯酶家族，并催化GPI-APs上聚糖部分的重塑。PGAP5催化活性是GPI-APs从ER有效输出的先决条件。我们的数据表明GPI聚糖作为ER输出信号，并提示由PGAP5介导的聚糖重塑调节早期分泌途径中的GPI-AP运输。
