title: GGAs: a family of ADP ribosylation factor-binding proteins related to adaptors and associated with the Golgi complex.
abstract: Formation of intracellular transport intermediates and selection of cargo molecules are mediated by protein coats associated with the cytosolic face of membranes. Here, we describe a novel family of ubiquitous coat proteins termed GGAs, which includes three members in humans and two in yeast. GGAs have a modular structure consisting of a VHS domain, a region of homology termed GAT, a linker segment, and a region with homology to the ear domain of gamma-adaptins. Immunofluorescence microscopy showed colocalization of GGAs with Golgi markers, whereas immunoelectron microscopy of GGA3 revealed its presence on coated vesicles and buds in the area of the TGN. Treatment with brefeldin A or overexpression of dominant-negative ADP ribosylation factor 1 (ARF1) caused dissociation of GGAs from membranes. The GAT region of GGA3 was found to: target a reporter protein to the Golgi complex; induce dissociation from membranes of ARF-regulated coats such as AP-1, AP-3, AP-4, and COPI upon overexpression; and interact with activated ARF1. Disruption of both GGA genes in yeast resulted in impaired trafficking of carboxypeptidase Y to the vacuole. These observations suggest that GGAs are components of ARF-regulated coats that mediate protein trafficking at the TGN.
authors.affiliation: Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Dell'Angelica
authors.forename: R
authors.initials: R
authors.lastname: Puertollano
authors.forename: C
authors.initials: C
authors.lastname: Mullins
authors.forename: R C
authors.initials: RC
authors.lastname: Aguilar
authors.forename: J D
authors.initials: JD
authors.lastname: Vargas
authors.forename: L M
authors.initials: LM
authors.lastname: Hartnell
authors.forename: J S
authors.initials: JS
authors.lastname: Bonifacino
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D033982:Adaptor Protein Complex gamma Subunits; D033942:Adaptor Proteins, Vesicular Transport; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A / Q000494:pharmacology; D002268:Carboxypeptidases / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D043402:Cathepsin A; D003001:Cloning, Molecular; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism / Q000648:ultrastructure; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; 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; D011993:Recombinant Fusion Proteins; D020126:Brefeldin A; D002268:Carboxypeptidases; C468629:CTSA protein, human; D043402:Cathepsin A; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors