title: A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome.
abstract: We have cloned and characterized members of a novel family of proteins, the GGAs. These proteins contain an NH(2)-terminal VHS domain, one or two coiled-coil domains, and a COOH-terminal domain homologous to the COOH-terminal "ear" domain of gamma-adaptin. However, unlike gamma-adaptin, the GGAs are not associated with clathrin-coated vesicles or with any of the components of the AP-1 complex. GGA1 and GGA2 are also not associated with each other, although they colocalize on perinuclear membranes. Immunogold EM shows that these membranes correspond to trans elements of the Golgi stack and the TGN. GST pulldown experiments indicate that the GGA COOH-terminal domains bind to a subset of the proteins that bind to the gamma-adaptin COOH-terminal domain. In yeast there are two GGA genes. Deleting both of these genes results in missorting of the vacuolar enzyme carboxypeptidase Y, and the cells also have a defective vacuolar morphology phenotype. These results indicate that the function of the GGAs is to facilitate the trafficking of proteins between the TGN and the vacuole, or its mammalian equivalent, the lysosome.
authors.affiliation: University of Cambridge, Department of Clinical Biochemistry, Wellcome Trust Centre for the Study of Molecular Mechanisms in Disease, Cambridge CB2 2XY, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Hirst
authors.forename: W W
authors.initials: WW
authors.lastname: Lui
authors.forename: N A
authors.initials: NA
authors.lastname: Bright
authors.forename: N
authors.initials: N
authors.lastname: Totty
authors.forename: M N
authors.initials: MN
authors.lastname: Seaman
authors.forename: M S
authors.initials: MS
authors.lastname: Robinson
mesh_terms: D020727:ADP-Ribosylation Factors; D033982:Adaptor Protein Complex gamma Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D001692:Biological Transport; D002268:Carboxypeptidases / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D043402:Cathepsin A; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation / Q000235:genetics; D009685:Nuclear Envelope / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014617:Vacuoles / Q000378:metabolism*
chemical_list: D033982:Adaptor Protein Complex gamma Subunits; D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; C407306:GGA adaptor proteins; C405944:GGA2 protein, human; D008565:Membrane Proteins; D011506:Proteins; D002268:Carboxypeptidases; C468629:CTSA protein, human; D043402:Cathepsin A; D020727:ADP-Ribosylation Factors