SUPPRESSORS OF THE CA2-SENSITIVE YEAST MUTANT (CSG2) IDENTIFY GENES INVOLVED IN SPHINGOLIPID BIOSYNTHESIS - CLONING AND CHARACTERIZATION OFSCS1, A GENE REQUIRED FOR SERINE PALMITOYLTRANSFERASE ACTIVITY()

Suppressor mutations in Saccharomyces cerevisiae that block Ca2+-induc ed death of csg2 mutant cells were investigated. These mutants, called scs mutants (suppresser of Ca2+ sensitivity), fall into seven complem entation groups (scs1-scs7). Ah mutant strains in two of the complemen tation groups (scs1 and scs2) simultaneously acquire a requirement for 10 mM Ca2+, whereas wild type grow with only trace amounts of Ca2+. S CS1 was cloned by complementation of its Ca2+-requiring phenotype and found to be homologous to a family of pyridoxal phosphate enzymes that catalyze acyltransfer reactions. Secondary phenotypes of the scs1 mut ants indicate that SCS1 is required for serine palmitoyltransferase ac tivity which catalyzes the first committed step in sphingolipid biosyn thesis (palmitoyl-CoA + serine --> 3-ketosphinganine + CoASH + CO2). O ther scs mutants as well as the csg2 null mutant have altered sphingol ipid metabolism. The data suggest that sphingolipid metabolism in yeas t is either regulated by Ca2+ and/or is required for Ca2+ homeostasis.