QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 17, Issue 3, 1410-1420, March 2006

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E05-11-1005v1 17/3/1410    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tashima, Y. Articles by Maeda, Y. Search for Related Content PubMed PubMed Citation Articles by Tashima, Y. Articles by Maeda, Y.

PGAP2 Is Essential for Correct Processing and Stable Expression of GPI-anchored Proteins

Yuko Tashima ^*, Ryo Taguchi , Chie Murata , Hisashi Ashida ^*, Taroh Kinoshita ^*, and Yusuke Maeda ^*

^* Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan

Submitted November 2, 2005; Revised December 27, 2005; Accepted January 4, 2006
Monitoring Editor: Howard Riezman

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.

Abbreviations used: BFA, brefeldin A; CHO, Chinese hamster ovary; GPI-AP, glycosylphosphatidylinositol-anchored protein; PGAP, post-GPI-attachment to proteins; PLA, phospholipase A; PLD, phospholipase D; TGN, trans-Golgi network.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Yusuke Maeda (ymaeda{at}biken.osaka-u.ac.jp) or Taroh Kinoshita (tkinoshi{at}biken.osaka-u.ac.jp).

This article has been cited by other articles:

				T. Kinoshita, M. Fujita, and Y. Maeda Biosynthesis, Remodelling and Functions of Mammalian GPI-anchored Proteins: Recent Progress J. Biochem., September 1, 2008; 144(3): 287 - 294. [Abstract] [Full Text] [PDF]

				K. Kajiwara, R. Watanabe, H. Pichler, K. Ihara, S. Murakami, H. Riezman, and K. Funato Yeast ARV1 Is Required for Efficient Delivery of an Early GPI Intermediate to the First Mannosyltransferase during GPI Assembly and Controls Lipid Flow from the Endoplasmic Reticulum Mol. Biol. Cell, May 1, 2008; 19(5): 2069 - 2082. [Abstract] [Full Text] [PDF]

				M. Umemura, M. Fujita, T. Yoko-o, A. Fukamizu, and Y. Jigami Saccharomyces cerevisiae CWH43 Is Involved in the Remodeling of the Lipid Moiety of GPI Anchors to Ceramides Mol. Biol. Cell, November 1, 2007; 18(11): 4304 - 4316. [Abstract] [Full Text] [PDF]

				T. Houjou, J. Hayakawa, R. Watanabe, Y. Tashima, Y. Maeda, T. Kinoshita, and R. Taguchi Changes in molecular species profiles of glycosylphosphatidylinositol anchor precursors in early stages of biosynthesis J. Lipid Res., July 1, 2007; 48(7): 1599 - 1606. [Abstract] [Full Text] [PDF]

				P. Orlean and A. K. Menon Thematic review series: Lipid Posttranslational Modifications. GPI anchoring of protein in yeast and mammalian cells, or: how we learned to stop worrying and love glycophospholipids J. Lipid Res., May 1, 2007; 48(5): 993 - 1011. [Abstract] [Full Text] [PDF]

				Y. Maeda, Y. Tashima, T. Houjou, M. Fujita, T. Yoko-o, Y. Jigami, R. Taguchi, and T. Kinoshita Fatty Acid Remodeling of GPI-anchored Proteins Is Required for Their Raft Association Mol. Biol. Cell, April 1, 2007; 18(4): 1497 - 1506. [Abstract] [Full Text] [PDF]

				M. Fujita, M. Umemura, T. Yoko-o, and Y. Jigami PER1 Is Required for GPI-Phospholipase A2 Activity and Involved in Lipid Remodeling of GPI-anchored Proteins Mol. Biol. Cell, December 1, 2006; 17(12): 5253 - 5264. [Abstract] [Full Text] [PDF]

				R. Bosson, M. Jaquenoud, and A. Conzelmann GUP1 of Saccharomyces cerevisiae Encodes an O-Acyltransferase Involved in Remodeling of the GPI Anchor Mol. Biol. Cell, June 1, 2006; 17(6): 2636 - 2645. [Abstract] [Full Text] [PDF]