title: Mutational analysis of SEC4 suggests a cyclical mechanism for the regulation of vesicular traffic.
abstract: Mutant alleles of SEC4, an essential gene required for the final stage of secretion in yeast, have been generated by in vitro mutagenesis. Deletion of the two cysteine residues at the C terminus of the protein results in a soluble non-functional protein, indicating that those two residues are required for normal localization of Sec4p to secretory vesicles and the plasma membrane. A mutant allele of SEC4 generated to mimic an activated, transforming allele of H-ras, as predicted, does not bind GTP. The presence of this allele in cells containing wild-type SEC4 causes a secretory defect and the accumulation of secretory vesicles. The results of genetic studies indicate that this allele behaves as a dominant loss of function mutant and as such prevents wild-type protein from functioning properly. We propose a model in which Sec4p cycles between an active and an inactive state in order to mediate the fusion of vesicles to the plasma membrane.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven CT 06510.
authors.forename: N C
authors.initials: NC
authors.lastname: Walworth
authors.forename: B
authors.initials: B
authors.lastname: Goud
authors.forename: A K
authors.initials: AK
authors.lastname: Kabcenell
authors.forename: P J
authors.initials: PJ
authors.lastname: Novick
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D002872:Chromosome Deletion; D003594:Cytoplasmic Granules / Q000502:physiology / Q000648:ultrastructure; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005799:Genes, Dominant; D005800:Genes, Fungal; D005804:Genes, Lethal; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure
chemical_list: D005656:Fungal Proteins; D019204:GTP-Binding Proteins