Synthesis of mannosylinositol phosphorylceramides is involved in maintenance of cell integrity of yeast S accharomyces cerevisiae

Summary Complex sphingolipids play important roles in many physiologically important events in yeast S accharomyces 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 ( S ur1 and C sh1). 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 S lt2, 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 M nn2. Moreover, the growth defect of MNN2 ‐repressed sur1Δ csh1Δ cells was enhanced by the deletion of SLT2 or RLM1 encoding a downstream target of S lt2. 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.