title: An essential function of sphingolipids in yeast cell division.
abstract: Ceramides are bioactive lipids and precursors to sphingolipids. They have been shown to take part in a wide variety of different physiological processes in eukaryotic organisms and are thought to be toxic at high concentrations. Ceramide is synthesized by condensation of the sphingoid base sphinganine and a fatty acyl CoA by ceramide synthases, a family of enzymes that differ in their specificity for the length of the acyl CoA substrate. We have engineered a yeast strain where the endogenous ceramide synthase has been replaced by one of the putative enzymes from cotton. As a result, the yeast strain produces C18 rather than C26 ceramides showing that the cotton protein is a bona fide ceramide synthase with specificity towards C18 acyl CoA. Strikingly, the accumulation of C18 ceramide is not toxic in Saccharomyces cerevisiae. This allows survival of the yeast after deletion of the normally essential AUR1 (inositol phosphorylceramide synthase) gene permitting us to address the essential roles of sphingolipids. Deletion of AUR1 allows cell growth, but leads to a defect in cytokinesis, which takes twice as long as in wild-type strains. Nuclear division and recruitment of septins is apparently not affected, but cytokinesis is delayed and cell separation is incomplete.
authors.affiliation: Department of Biochemistry and NCCR Chemical Biology, University of Geneva, CH-1211 Geneva 4, Switzerland.
authors.forename: Sharon
authors.initials: S
authors.lastname: Epstein
authors.forename: Guillaume A
authors.initials: GA
authors.lastname: Castillon
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Qin
authors.forename: Howard
authors.initials: H
authors.lastname: Riezman
mesh_terms: D002455:Cell Division; D002518:Ceramides / Q000378:metabolism*; D017353:Gene Deletion; D003368:Gossypium / Q000201:enzymology / Q000235:genetics; D006602:Hexosyltransferases / Q000235:genetics / Q000378:metabolism*; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways / Q000235:genetics; D050296:Microbial Viability; D008954:Models, Biological; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017422:Sequence Analysis, DNA
chemical_list: D002518:Ceramides; D011994:Recombinant Proteins; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D006602:Hexosyltransferases; C088714:phosphatidylinositol-ceramide phosphoinositol transferase