title: Involvement of long chain fatty acid elongation in the trafficking of secretory vesicles in yeast.
abstract: Members of the synaptobrevin/VAMP family of v-SNAREs are thought to be essential for vesicle docking and exocytosis in both lower and higher eukaryotes. Here, we describe yeast mutants that appear to bypass the known v-SNARE requirement in secretion. Recessive mutations in either VBM1 or VBM2, which encode related ER-localized membrane proteins, allow yeast to grow normally and secrete in the absence of Snc v-SNAREs. These mutants show selective alterations in protein transport, resulting in the differential trafficking and secretion of certain protein cargo. Yet, processing of the vacuolar marker, carboxypeptidase Y, and the secreted protein, invertase, appear normal in these mutants indicating that general protein trafficking early in the pathway is unaffected. Interestingly, VBM1 and VBM2 are allelic to ELO3 and ELO2, two genes that have been shown recently to mediate the elongation of very long chain fatty acids and subsequent ceramide and inositol sphingolipid synthesis. Thus, the v-SNARE requirement in constitutive exocytosis is abrogated by mutations in early components of the secretory pathway that act at the level of lipid synthesis to affect the ability of secretory vesicles to sort and deliver protein cargo.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: D
authors.initials: D
authors.lastname: David
authors.forename: S
authors.initials: S
authors.lastname: Sundarababu
authors.forename: J E
authors.initials: JE
authors.lastname: Gerst
mesh_terms: D000483:Alleles; D001693:Biological Transport, Active; D002268:Carboxypeptidases / Q000378:metabolism; D043402:Cathepsin A; D002518:Ceramides / Q000096:biosynthesis; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005089:Exocytosis; D005227:Fatty Acids / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005800:Genes, Fungal; D006026:Glycoside Hydrolases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation; D015388:Organelles / Q000378:metabolism / Q000648:ultrastructure; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids / Q000096:biosynthesis; D033921:Vesicular Transport Proteins; D043324:beta-Fructofuranosidase
chemical_list: D002518:Ceramides; D005227:Fatty Acids; D005656:Fungal Proteins; C066709:GAS1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D033921:Vesicular Transport Proteins; D006026:Glycoside Hydrolases; D043324:beta-Fructofuranosidase; D002268:Carboxypeptidases; D043402:Cathepsin A