title: Determination and physiological roles of the glycosylphosphatidylinositol lipid remodelling pathway in yeast.
abstract: 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 inositolphosphoryl-ceramide 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.
authors: Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Higashi, Tsukuba 305-8566, Japan. t.yoko-o@aist.go.jp
authors: Takehiko
authors: T
authors: Yoko-O
authors: Daisuke
authors: D
authors: Ichikawa
authors: Yasunori
authors: Y
authors: Miyagishi
authors: Akiko
authors: A
authors: Kato
authors: Mariko
authors: M
authors: Umemura
authors: Kumiko
authors: K
authors: Takase
authors: Moonjin
authors: M
authors: Ra
authors: Kazutaka
authors: K
authors: Ikeda
authors: Ryo
authors: R
authors: Taguchi
authors: Yoshifumi
authors: Y
authors: Jigami
mesh_terms: D055162:Biocatalysis / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014364:Tryptophan / Q000494:pharmacology
chemical_list: D003470:Culture Media; D003902:Detergents; D017261:Glycosylphosphatidylinositols; D029701:Saccharomyces cerevisiae Proteins; D014364:Tryptophan