title: The yeast VPS5/GRD2 gene encodes a sorting nexin-1-like protein required for localizing membrane proteins to the late Golgi.
abstract: Genetic analysis of late Golgi membrane protein localization in Saccharomyces cerevisiae has uncovered a large number of genes (called GRD) that are required for retention of A-ALP, a model late Golgi membrane protein. Here we describe one of the GRD genes, VPSS/GRD2, that encodes a hydrophilic protein similar to human sorting nexin-1, a protein involved in trafficking of the epidermal growth factor receptor. In yeast cells containing a vps5 null mutation the late Golgi membrane proteins A-ALP and Kex2p were rapidly mislocalized to the vacuolar membrane. A-ALP was delivered to the vacuole in vps5 mutants in a manner independent of a block in the early endocytic pathway. vps5 null mutants also exhibited defects in both vacuolar morphology and in sorting of a soluble vacuolar protein, carboxypeptidase Y. The latter defect is apparently due to an inability to localize the carboxypeptidase Y sorting receptor, Vps10p, to the Golgi since it is rapidly degraded in the vacuole in vps5 mutants. Fractionation studies indicate that Vps5p is distributed between a free cytosolic pool and a particulate fraction containing Golgi, transport vesicles, and possibly endosomes, but lacking vacuolar membranes. Immunofluorescence microscopy experiments show that the membrane-associated pool of Vps5p localizes to an endosome-like organelle that accumulates in the class E vps27 mutant. These results support a model in which Vps5p is required for retrieval of membrane proteins from a prevacuolar/late endosomal compartment back to the late Golgi apparatus.
authors.affiliation: Division of Biological Sciences, University of Missouri, Columbia 65211, USA. nothwehr@biosci.mbp.missouri.edu
authors.forename: S F
authors.initials: SF
authors.lastname: Nothwehr
authors.forename: A E
authors.initials: AE
authors.lastname: Hindes
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002458:Cell Fractionation; D003001:Cloning, Molecular; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D017930:Genes, Reporter; D006056:Golgi Apparatus / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014617:Vacuoles / Q000737:chemistry / Q000378:metabolism; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D005656:Fungal Proteins; C087335:PEP1 protein, S cerevisiae; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C106932:VPS5 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D066246:ErbB Receptors; D000469:Alkaline Phosphatase