title: PGAP2 is essential for correct processing and stable expression of GPI-anchored proteins.
abstract: 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.
authors.affiliation: Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tashima
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Chie
authors.initials: C
authors.lastname: Murata
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ashida
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Maeda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018958:CD55 Antigens / Q000378:metabolism; D018957:CD59 Antigens / Q000378:metabolism; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D016895:Culture Media, Serum-Free; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051381:Rats
chemical_list: D018958:CD55 Antigens; D018957:CD59 Antigens; D016895:Culture Media, Serum-Free; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D009687:Nuclear Proteins; C101463:PGAP2 protein, rat; D010710:Phosphates; D007294:Inositol