GPI Glycan Remodeling by PGAP5 Regulates Transport of GPI-Anchored Proteins from the ER to the Golgi

• Published in: Cell 2009-10, Vol.139 (2), p.352-365
• Main Authors: Fujita, Morihisa, Maeda, Yusuke, Ra, Moonjin, Yamaguchi, Yoshiki, Taguchi, Ryo, Kinoshita, Taroh
• Format: Article
• Language: English
• Subjects: Animals; CELLBIO; Endoplasmic Reticulum - metabolism; Glycoproteins - metabolism; Glycosylphosphatidylinositols - metabolism; Golgi Apparatus - metabolism; Humans; Mice; Phosphoric Diester Hydrolases - genetics; Phosphoric Diester Hydrolases - metabolism; Polysaccharides - metabolism
• ISSN: 0092-8674; 1097-4172
• 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.