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MBC in Press, published online ahead of print August 29, 2007
Mol. Biol. Cell 10.1091/mbc.E07-05-0482

A more recent version of this article appeared on November 1, 2007
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Submitted on May 22, 2007
Revised on August 9, 2007
Accepted on August 17, 2007

Saccharomyces cerevisiae CWH43 Is Involved in the Remodeling of the Lipid Moiety of GPI Anchors to Ceramides

Mariko Umemura,*{dagger} Morihisa Fujita,* Takehiko Yoko-o,* Akiyoshi Fukamizu,{ddagger} and Yoshifumi Jigami*{dagger}

*Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan; {dagger}Graduate School of Life and Environmental Science, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan; {ddagger}Center for Tsukuba Advanced Research Alliance (TARA), Graduate School of Life and Environmental Science, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan

Monitoring Editor: Sean Munro

The glycosylphosphatidylinositol (GPI)-anchored proteins are subjected to lipid remodeling during their biosynthesis. In the yeast S. cerevisiae, the mature GPI-anchored proteins contain mainly ceramide or diacylglycerol with a saturated long fatty acid, whereas conventional phosphatidylinositol (PI) used for GPI biosynthesis contains an unsaturated fatty acid. Here, we report that S. cerevisiae Cwh43p, whose N-terminal region contains a sequence homologous to mammalian PGAP2, is involved in the remodeling of the lipid moiety of GPI anchors to ceramides. In cwh43 disruptant cells, the PI moiety of the GPI-anchored protein contains a saturated long fatty acid and lyso-PI but not inositolphosphorylceramides, which are the main lipid moieties of GPI-anchored proteins from wild-type cells. Moreover, the C-terminal region of Cwh43p (Cwh43-C), which is not present in PGAP2, is essential for the ability to remodel GPI lipids to ceramides. The N-terminal region of Cwh43p (Cwh43-N) is associated with Cwh43-C and enhanced the lipid remodeling to ceramides by Cwh43-C. Our results also indicate that mouse FRAG1 and C130090K23, which are homologous to Cwh43-N and -C, respectively, share these activities.


Address correspondence to: Yoshifumi Jigami (jigami.yoshi{at}aist.go.jp)




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