RECEPTOR-MEDIATED PROTEIN SORTING TO THE VACUOLE IN YEAST - ROLES FORA PROTEIN-KINASE, A LIPID KINASE AND GTP-BINDING PROTEINS

In this review we summarize the structural and functional characterist ics of the VPS (vacuolar protein sorting) gene products that have prov ided insight into the regulatory interactions and molecular mechanisms underlying protein sorting pathways in eukaryotic cells. Genetic sele ctions in yeast have resulted in the identification of more than 40 ge nes required for the vesicle-mediated sorting of proteins to the lysos ome-like vacuole. Molecular characterization of these VPS gene product s has revealed a number of biochemical activities involved in this pro cess. Analogous to the mannose-6-phosphate receptors in mammalian cell s, the VPS10 gene encodes a transmembrane sorting receptor for the yea st vacuolar hydrolase carboxypeptidase Y. The VPS15 and VPS34 genes en code components of a novel signal transduction complex essential for t he delivery of soluble vacuolar hydrolases. VPS15 and VPS34 encode a s erine/threonine protein kinase and a phosphatidylinositol 3-kinase, re spectively, that interact at the cytoplasmic face of an intracellular membrane compartment, most likely corresponding to the late Golgi. Oth er VPS gene products have homologues that are involved in membrane tra fficking pathways: The VPS1 and VPS21 genes encode GTPases of the dyna min and rab families, respectively, and the products of the VPS33, VPS 45, and PEP12/VPS6 genes are homologues of proteins involved in regula ted synaptic vesicle exocytosis. The VPS gene products constitute comp onents of a molecular apparatus responsible for the recognition, packa ging, and vesicular transport of proteins to the vacuole in yeast.