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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
*Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan;
Graduate School of Life and Environmental Science, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan;
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.
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