Suppressors of the Ca(2+)-sensitive yeast mutant (csg2) identify genes involved in sphingolipid biosynthesis. Cloning and characterization of SCS1, a gene required for serine palmitoyltransferase activity.
Suppressor mutations in Saccharomyces cerevisiae that block Ca(2+)-induced death of csg2 mutant cells were investigated. These mutants, called scs mutants (suppressor of Ca2+ sensitivity), fall into seven complementation groups (scs1-scs7). All mutant strains in two of the complementation groups (scs1 and scs2) simultaneously acquire a requirement for 10 mM Ca2+, whereas wild type grow with only trace amounts of Ca2+. SCS1 was cloned by complementation of its Ca(2+)-requiring phenotype and found to be homologous to a family of pyridoxal phosphate enzymes that catalyze acyltransfer reactions. Secondary phenotypes of the scs1 mutants indicate that SCS1 is required for serine palmitoyltransferase activity which catalyzes the first committed step in sphingolipid biosynthesis (palmitoyl-CoA + serine-->3-ketosphinganine+CoASH+CO2). Other scs mutants as well as the csg2 null mutant have altered sphingolipid metabolism. The data suggest that sphingolipid metabolism in yeast is either regulated by Ca2+ and/or is required for Ca2+ homeostasis.
Zhao
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Department of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Beeler
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Dunn
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D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D005800:Genes, Fungal / Q000235:genetics*; D007294:Inositol / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D051102:Serine C-Palmitoyltransferase; D013107:Sphingolipids / Q000096:biosynthesis*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013489:Suppression, Genetic
D013107:Sphingolipids; D007294:Inositol; D000217:Acyltransferases; D051102:Serine C-Palmitoyltransferase; C012491:phytosphingosine; D013110:Sphingosine