A family of ADP-ribosylation factor effectors that can alter membrane transport through the trans-Golgi.
A family of three structurally related proteins were cloned from human cDNA libraries by their ability to interact preferentially with the activated form of human ADP-ribosylation factor 3 (ARF3) in two-hybrid assays. The specific and GTP-dependent binding was later confirmed through direct protein binding of recombinant proteins. The three proteins share large ( approximately 300 residues) domains at their N termini that are 60-70% identical to each other and a shorter (73 residues) domain at their C termini with 70% homology to the C-terminal "ear" domain of gamma-adaptin. Although GGA1 is found predominantly as a soluble protein by cell fractionation, all three proteins were found to localize to the trans-Golgi network (TGN) by indirect immunofluorescence. The binding of GGAs to TGN was sensitive to brefeldin A, consistent with this being an ARF-dependent event. Thus, these proteins have been named Golgi-localizing, gamma-adaptin ear homology domain, ARF-binding proteins, or GGAs. The finding that overexpression of GGAs was sufficient to alter the distribution of markers of the TGN (TGN38 and mannose 6-phosphate receptors) led us to propose that GGAs are effectors for ARFs that function in the regulation of membrane traffic through the TGN.
Boman
A L
AL
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322-3050, USA.
Zhang
C j
Cj
Zhu
X
X
Kahn
R A
RA
D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D019084:Fluorescent Antibody Technique, Indirect; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007425:Intracellular Membranes / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D008969:Molecular Sequence Data; D009928:Organ Specificity; D017434:Protein Structure, Tertiary; D011506:Proteins; D051381:Rats; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques; D015003:Yeasts
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; C407306:GGA adaptor proteins; C405944:GGA2 protein, human; D011506:Proteins; C116687:ARF3 protein, human; C492129:Arf3 protein, rat; D020727:ADP-Ribosylation Factors