title: Sphingolipids are potential heat stress signals in Saccharomyces.
abstract: The ability of organisms to quickly respond to stresses requires the activation of many intracellular signal transduction pathways. The sphingolipid intermediate ceramide is thought to be particularly important for activating and coordinating signaling pathways during mammalian stress responses. Here we present the first evidence that ceramide and other sphingolipid intermediates are signaling molecules in the Saccharomyces cerevisiae heat stress response. Our data show a 2-3-fold transient increase in the concentration of C18-dihydrosphingosine and C18-phytosphingosine, more than a 100-fold transient increase in C20-dihydrosphingosine and C20-phytosphingosine, and a more stable 2-fold increase in ceramide containing C18-phytosphingosine and a 5-fold increase in ceramide containing C20-phytosphingosine following heat stress. Treatment of cells with dihydrosphingosine activates transcription of the TPS2 gene encoding a subunit of trehalose synthase and causes trehalose, a known thermoprotectant, to accumulate. Dihydrosphingosine induces expression of a STRE-LacZ reporter gene, showing that the global stress response element, STRE, found in many yeast promoter sequences can be activated by sphingolipid signals. The TPS2 promoter contains four STREs that may mediate dihydrosphingosine responsiveness. Using genetic and other approaches it should be possible to identify sphingolipid signaling pathways in S. cerevisiae and quantify the importance of each during heat stress.
authors.affiliation: Department of Biochemistry and the Lucille P. Markey Cancer Center, University of Kentucky Medical Center, Lexington, Kentucky 40536-0084, USA. bobd@pop.uky.edu
authors.forename: R C
authors.initials: RC
authors.lastname: Dickson
authors.forename: E E
authors.initials: EE
authors.lastname: Nagiec
authors.forename: M
authors.initials: M
authors.lastname: Skrzypek
authors.forename: P
authors.initials: P
authors.lastname: Tillman
authors.forename: G B
authors.initials: GB
authors.lastname: Wells
authors.forename: R L
authors.initials: RL
authors.lastname: Lester
mesh_terms: D047630:Depsipeptides; D005656:Fungal Proteins / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D005964:Glucosyltransferases / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics*; D006358:Hot Temperature; D009097:Multienzyme Complexes / Q000235:genetics*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism*; D014158:Transcription, Genetic; D014199:Trehalose / Q000378:metabolism
chemical_list: D047630:Depsipeptides; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D009097:Multienzyme Complexes; D010456:Peptides, Cyclic; D013107:Sphingolipids; C071398:aureobasidin A; D014199:Trehalose; D005964:Glucosyltransferases; C085814:trehalose-6-phosphate synthase-phosphatase complex; D010744:Phosphoric Monoester Hydrolases