SUR1 (CSG1 BCL21), A GENE NECESSARY FOR GROWTH OF SACCHAROMYCES-CEREVISIAE IN THE PRESENCE OF HIGH CA2+ CONCENTRATIONS AT 37-DEGREES-C, IS REQUIRED FOR MANNOSYLATION OF INOSITOLPHOSPHORYLCERAMIDE/

Saccharomyces cerevisiae cells require two genes, CSG1/SUR1 and CSG2, for growth in 50 mM Ca2+, but not 50 mM Sr2+. CSG2 was previously show n to be required for the mannosylation of inositol-phosphorylceramide (IPC) to form mannosylinositolphosphorylceramide (MIPC). Here we demon strate that SUR1/CSG1 is both genetically and biochemically related to CSG2. Like CSG2, SUR1/CSG1 is required for IPC mannosylation. A 93-am ino acid stretch of Csg1p shows 29% identity with the alpha-1, 6-manno syltransferase encoded by OCH1. The SUR1/CSG1 gene is a dose-dependent suppressor of the Ca2+-sensitive phenotype of the csg2 mutant, but ov erexpression of CSG2 does not suppress the Ca2+ sensitivity of the csg 1 mutant. The csg1 and csg2 mutants display normal growth in YPD, indi cating that mannosylation elf sphingolipids is not essential.]Increase d osmolarity of the growth medium increases the Ca2+ tolerance of csg1 and csg2 mutant cells suggesting that altered cell wall synthesis cau ses Ca2+-induced death. Hydroxylation of IPC-C to form IPC-D requires CCC2, a gene encoding an intracellular cellular Cu transporter. Increa sed expression of CCC2 or increased Cu2+ concentration in the growth m edium enhances the Ca2+ tolerance of csg1 mutants, suggesting that acc umulation of IPC-C renders csg1 cells Ca2+ sensitive.