title: Receptor-mediated protein sorting to the vacuole in yeast: roles for a protein kinase, a lipid kinase and GTP-binding proteins.
abstract: In this review we summarize the structural and functional characteristics of the VPS (vacuolar protein sorting) gene products that have provided insight into the regulatory interactions and molecular mechanisms underlying protein sorting pathways in eukaryotic cells. Genetic selections in yeast have resulted in the identification of more than 40 genes required for the vesicle-mediated sorting of proteins to the lysosome-like vacuole. Molecular characterization of these VPS gene products has revealed a number of biochemical activities involved in this process. Analogous to the mannose-6-phosphate receptors in mammalian cells, the VPS10 gene encodes a transmembrane sorting receptor for the yeast vacuolar hydrolase carboxypeptidase Y. The VPS15 and VPS34 genes encode components of a novel signal transduction complex essential for the delivery of soluble vacuolar hydrolases. VPS15 and VPS34 encode a serine/ threonine protein kinase and a phosphatidylinositol 3-kinase, respectively, that interact at the cytoplasmic face of an intracellular membrane compartment, most likely corresponding to the late Golgi. Other VPS gene products have homologues that are involved in membrane trafficking pathways: The VPSI and VPS21 genes encode GTPases of the dynamin and rab families, respectively, and the products of the VPS33, VPS45, and PEP12/VPS6 genes are homologues of proteins involved in regulated synaptic vesicle exocytosis. The VPS gene products constitute components of a molecular apparatus responsible for the recognition, packaging, and vesicular transport of proteins to the vacuole in yeast.
authors.affiliation: Division of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla 92093-0668, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Stack
authors.forename: B
authors.initials: B
authors.lastname: Horazdovsky
authors.forename: S D
authors.initials: SD
authors.lastname: Emr
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism; D005656:Fungal Proteins / Q000096:biosynthesis / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005800:Genes, Fungal; D008247:Lysosomes / Q000378:metabolism; D008322:Mammals; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D002966:Clathrin; D005656:Fungal Proteins; D019204:GTP-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011494:Protein Kinases; D017527:Receptor, IGF Type 2