PGAP2 is essential for correct processing and stable expression of GPI-anchored proteins

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...

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology of the cell 2006-03, Vol.17 (3), p.1410-1420
Main Authors: Tashima, Yuko, Taguchi, Ryo, Murata, Chie, Ashida, Hisashi, Kinoshita, Taroh, Maeda, Yusuke
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
CD55 Antigens - metabolism
CD59 Antigens - metabolism
Cell Membrane - metabolism
Cells, Cultured
CHO Cells
Cloning, Molecular
Cricetinae
Cricetulus
Culture Media, Serum-Free
Endoplasmic Reticulum - metabolism
Glycosylphosphatidylinositols - biosynthesis
Glycosylphosphatidylinositols - chemistry
Glycosylphosphatidylinositols - metabolism
Humans
Inositol - metabolism
Membrane Proteins - metabolism
Molecular Sequence Data
Mutation - genetics
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Phosphates - metabolism
Protein Processing, Post-Translational
Protein Transport
Rats
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E05-11-1005