Determination and physiological roles of the glycosylphosphatidylinositol lipid remodelling pathway in yeast

Authors

  • Takehiko Yoko-o,

    Corresponding author
    1. Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
    2. Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
    • For correspondence. E-mail t.yoko-o@aist.go.jp; Tel. (+81) 29 861 6239; Fax (+81) 29 861 6239.

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  • Daisuke Ichikawa,

    1. Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
    2. Graduate School of Life and Environmental Science, University of Tsukuba, Tsukuba, Japan
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  • Yasunori Miyagishi,

    1. Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
    2. Graduate School of Life and Environmental Science, University of Tsukuba, Tsukuba, Japan
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  • Akiko Kato,

    1. Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
    2. Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
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  • Mariko Umemura,

    1. Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
    2. The School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
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  • Kumiko Takase,

    1. Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
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  • Moonjin Ra,

    1. Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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  • Kazutaka Ikeda,

    1. Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    2. Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
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  • Ryo Taguchi,

    1. Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    2. Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Aichi, Japan
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  • Yoshifumi Jigami

    1. Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
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Summary

In the yeast Saccharomyces cerevisiae, glycosylphosphatidylinositol (GPI)-anchored proteins play important roles in cell wall biogenesis/assembly and the formation of lipid microdomains. The lipid moieties of mature GPI-anchored proteins in yeast typically contain either ceramide moieties or diacylglycerol. Recent studies have identified that the GPI phospholipase A2 Per1p and O-acyltransferase Gup1p play essential roles in diacylglycerol-type lipid remodelling of GPI-anchored proteins, while Cwh43p is involved in the remodelling of lipid moieties to ceramide. It has been generally proposed that phosphatidylinositol with diacylglycerol containing a C26 saturated fatty acid, which is generated by the sequential activity of Per1p and Gup1p, is converted to inositolphosphorylceramide by Cwh43p. In this report, we constructed double-mutant strains defective in lipid remodelling and investigated their growth phenotypes and the lipid moieties of GPI-anchored proteins. Based on our analyses of single- and double-mutants of proteins involved in lipid remodelling, we demonstrate that an alternative pathway, in which lyso-phosphatidylinositol generated by Per1p is used as a substrate for Cwh43p, is involved in the remodelling of GPI lipid moieties to ceramide when the normal sequential pathway is inhibited. In addition, mass spectrometric analysis of lipid species of Flag-tagged Gas1p revealed that Gas1p contains ceramide moieties in its GPI anchor.

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