title: The sorting receptor for yeast vacuolar carboxypeptidase Y is encoded by the VPS10 gene.
abstract: The S. cerevisiae VPS10 (vacuolar protein sorting) gene encodes a type I transmembrane protein of 1577 amino acids required for the sorting of the soluble vacuolar protein carboxypeptidase Y (CPY). Mutations in VPS10 result in the selective missorting and secretion of CPY; all other vacuolar proteins tested are delivered to the vacuole in vps10 mutants. Chemical cross-linking studies demonstrate that Vps10p and the Golgi-modified precursor form of CPY directly interact. A single amino acid change in the CPY vacuolar sorting signal prevents this interaction. Vps10p also interacts with a hybrid protein containing the CPY sorting signal fused to the normally secreted enzyme invertase. Subcellular fractionation indicates that the majority of Vps10p is localized to a late Golgi compartment where vacuolar proteins are sorted. We propose that VPS10 encodes a CPY sorting receptor that executes multiple rounds of sorting by cycling between the late Golgi and a prevacuolar endosome-like compartment.
authors.affiliation: Division of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla 92093-0668.
authors.forename: E G
authors.initials: EG
authors.lastname: Marcusson
authors.forename: B F
authors.initials: BF
authors.lastname: Horazdovsky
authors.forename: J L
authors.initials: JL
authors.lastname: Cereghino
authors.forename: E
authors.initials: E
authors.lastname: Gharakhanian
authors.forename: S D
authors.initials: SD
authors.lastname: Emr
mesh_terms: D000595:Amino Acid Sequence; D002268:Carboxypeptidases / Q000032:analysis / Q000378:metabolism*; D043402:Cathepsin A; D003001:Cloning, Molecular; D005656:Fungal Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005800:Genes, Fungal / Q000235:genetics*; D005816:Genetic Complementation Test; D006031:Glycosylation; D006056:Golgi Apparatus / Q000737:chemistry; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D011956:Receptors, Cell Surface / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013104:Spheroplasts / Q000737:chemistry; D014617:Vacuoles / Q000737:chemistry / Q000378:metabolism*; D033921:Vesicular Transport Proteins
chemical_list: D005656:Fungal Proteins; D008565:Membrane Proteins; C087335:PEP1 protein, S cerevisiae; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D002268:Carboxypeptidases; D043402:Cathepsin A; C499283:PRC1 protein, S cerevisiae; C022633:serine carboxypeptidase