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

Vol. 18, Issue 4, 1497-1506, April 2007

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-10-0885v1 18/4/1497    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 Maeda, Y. Articles by Kinoshita, T. Search for Related Content PubMed PubMed Citation Articles by Maeda, Y. Articles by Kinoshita, T.

Fatty Acid Remodeling of GPI-anchored Proteins Is Required for Their Raft Association

Yusuke Maeda^*, Yuko Tashima^*, Toshiaki Houjou, Morihisa Fujita, Takehiko Yoko-o, Yoshifumi Jigami, Ryo Taguchi, and Taroh Kinoshita^*

*Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Graduate School of Medicine, University of Tokyo, Bunkyoku, Tokyo 113-0033, Japan; and Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan

Submitted October 2, 2006; Revised January 26, 2006; Accepted February 1, 2007
Monitoring Editor: Reid Gilmore

Whereas most of the cellular phosphatidylinositol (PI) contain unsaturated fatty chains and are excluded from rafts, GPI-anchored proteins (APs) unusually contain two saturated fatty chains in their PI moiety, and they are typically found within lipid rafts. However, the origin of the saturated chains and whether they are essential for raft association are unclear. Here, we report that GPI-APs, with two saturated fatty chains, are generated from those bearing an unsaturated chain by fatty acid remodeling that occurs most likely in the Golgi and requires post-GPI-attachment to proteins (PGAP)2 and PGAP3. The surface GPI-APs isolated from the PGAP2 and -3 double-mutant Chinese hamster ovary (CHO) cells had unsaturated chains, such as oleic, arachidonic, and docosatetraenoic acids in the sn-2 position, whereas those from wild-type CHO cells had exclusively stearic acid, a saturated chain, indicating that the sn-2 chain is exchanged to a saturated chain. We then assessed the association of GPI-APs with lipid rafts. Recovery of unremodeled GPI-APs from the double-mutant cells in the detergent-resistant membrane fraction was very low, indicating that GPI-APs become competent to be incorporated into lipid rafts by PGAP3- and PGAP2-mediated fatty acid remodeling. We also show that the remodeling requires the preceding PGAP1-mediated deacylation from inositol of GPI-APs in the endoplasmic reticulum.

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

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

Abbreviations used: AP, anchored protein; CHO, Chinese hamster ovary; DAF, decay accelerating factor; DRM, detergent-resistant membrane; ER, endoplasmic reticulum; PGAP, post-GPI-attachment to proteins; PI, phosphatidylinositol; PLA, phospholipase A

This article has been cited by other articles:

				A. Hasegawa, L. F. Sogo, M. Tan, and C. Sutterlin Host Complement Regulatory Protein CD59 Is Transported to the Chlamydial Inclusion by a Golgi Apparatus-Independent Pathway Infect. Immun., April 1, 2009; 77(4): 1285 - 1292. [Abstract] [Full Text] [PDF]

				S. Paladino, S. Lebreton, S. Tivodar, V. Campana, R. Tempre, and C. Zurzolo Different GPI-attachment signals affect the oligomerisation of GPI-anchored proteins and their apical sorting J. Cell Sci., December 15, 2008; 121(24): 4001 - 4007. [Abstract] [Full Text] [PDF]

				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]

				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]

				Y. Ueda, R. Yamaguchi, M. Ikawa, M. Okabe, E. Morii, Y. Maeda, and T. Kinoshita PGAP1 Knock-out Mice Show Otocephaly and Male Infertility J. Biol. Chem., October 19, 2007; 282(42): 30373 - 30380. [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]