title: Synthesis of mannosylinositol phosphorylceramides is involved in maintenance of cell integrity of yeast Saccharomyces cerevisiae.
abstract: Complex sphingolipids play important roles in many physiologically important events in yeast Saccharomyces cerevisiae. In this study, we screened yeast mutant strains showing a synthetic lethal interaction with loss of mannosylinositol phosphorylceramide (MIPC) synthesis and found that a specific group of glycosyltransferases involved in the synthesis of mannan-type N-glycans is essential for the growth of cells lacking MIPC synthases (Sur1 and Csh1). The genetic interaction was also confirmed by repression of MNN2, which encodes alpha-1,2-mannosyltransferase that synthesizes mannan-type N-glycans, by a tetracycline-regulatable system. MNN2-repressed sur1Δ csh1Δ cells exhibited high sensitivity to zymolyase treatment, and caffeine and sodium dodecyl sulfate (SDS) strongly inhibited the growth of sur1Δ csh1Δ cells, suggesting impairment of cell integrity due to the loss of MIPC synthesis. The phosphorylated form of Slt2, a mitogen-activated protein (MAP) kinase activated by impaired cell integrity, increased in sur1Δ csh1Δ cells, and this increase was dramatically enhanced by the repression of Mnn2. Moreover, the growth defect of MNN2-repressed sur1Δ csh1Δ cells was enhanced by the deletion of SLT2 or RLM1 encoding a downstream target of Slt2. These results indicated that loss of MIPC synthesis causes impairment of cell integrity, and this effect is enhanced by impaired synthesis of mannan-type N-glycans.
authors.affiliation: Department of Chemistry, Faculty of Sciences, Kyushu University, 6-10-1, Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tani
mesh_terms: D055786:Gene Knockout Techniques; D006028:Glycosphingolipids / Q000096:biosynthesis*; D016695:Glycosyltransferases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism
chemical_list: D006028:Glycosphingolipids; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; C479822:mannosylinositol phosphoylceramide; D016695:Glycosyltransferases