Protein sorting in yeast: mutants defective in vacuole biogenesis mislocalize vacuolar proteins into the late secretory pathway.
We have devised a genetic selection for mutant yeast cells that fail to properly deliver the vacuolar glycoprotein CPY to the lysosome-like vacuole. This has allowed us to identify mutations in eight VPL complementation groups that result in aberrant secretion of up to approximately 90% of the immunoreactive CPY. Other soluble vacuolar proteins are also affected by each vpl mutation, demonstrating that a sorting system for multiple vacuolar proteins exists in yeast. Mislocalized CPY apparently traverses late stages of the secretory pathway, since a vesicle-accumulating sec1 mutation prevents secretion of this protein. Despite the presence of abnormal membrane-enclosed organelles in some of the vpl mutants, maturation and secretion of invertase are not substantially perturbed. Thus vpl mutations define a new class of genes that encode products required for sorting of newly synthesized vacuolar proteins from secretory proteins during their transit through the yeast secretory pathway.
D016282:Aspartic Acid Endopeptidases; D002268:Carboxypeptidases / Q000378:metabolism*; D043402:Cathepsin A; D010450:Endopeptidases / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D005800:Genes, Fungal; D006026:Glycoside Hydrolases / Q000378:metabolism; D008361:Mannosidases / Q000378:metabolism; D008854:Microscopy, Electron; D009154:Mutation; D009940:Organoids / Q000378:metabolism*; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins; D012697:Serine Endopeptidases; D014617:Vacuoles / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D043323:alpha-Mannosidase; D043324:beta-Fructofuranosidase
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D006026:Glycoside Hydrolases; D008361:Mannosidases; D043323:alpha-Mannosidase; D043324:beta-Fructofuranosidase; D002268:Carboxypeptidases; D010450:Endopeptidases; D043402:Cathepsin A; C499283:PRC1 protein, S cerevisiae; C022633:serine carboxypeptidase; D012697:Serine Endopeptidases; C023302:yeast proteinase B; C022325:aspartic proteinase A; C499267:PEP4 protein, S cerevisiae; D016282:Aspartic Acid Endopeptidases