title: Translocation of activator of G-protein signaling 3 to the Golgi apparatus in response to receptor activation and its effect on the trans-Golgi network.
abstract: Group II activators of G-protein signaling play diverse functional roles through their interaction with Gαi, Gαt, and Gαo via a G-protein regulatory (GPR) motif that serves as a docking site for Gα-GDP. We recently reported the regulation of the AGS3-Gαi signaling module by a cell surface, seven-transmembrane receptor. Upon receptor activation, AGS3 reversibly dissociates from the cell cortex, suggesting that it may function as a signal transducer with downstream signaling implications, and this question is addressed in the current report. In HEK-293 and COS-7 cells expressing the α2A/D-AR and Gαi3, receptor activation resulted in the translocation of endogenous AGS3 and AGS3-GFP from the cell cortex to a juxtanuclear region, where it co-localized with markers of the Golgi apparatus (GA). The agonist-induced translocation of AGS3 was reversed by the α2-AR antagonist rauwolscine. The TPR domain of AGS3 was required for agonist-induced translocation of AGS3 from the cell cortex to the GA, and the translocation was blocked by pertussis toxin pretreatment or by the phospholipase Cβ inhibitor U73122. Agonist-induced translocation of AGS3 to the GA altered the functional organization and protein sorting at the trans-Golgi network. The regulated movement of AGS3 between the cell cortex and the GA offers unexpected mechanisms for modulating protein secretion and/or endosome recycling events at the trans-Golgi network.
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Sukru S
authors.initials: SS
authors.lastname: Oner
authors.forename: Ali
authors.initials: A
authors.lastname: Vural
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lanier
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D000068438:Brimonidine Tartrate; D019556:COS Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D021601:trans-Golgi Network / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C525615:GPSM1 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D011810:Quinoxalines; D011956:Receptors, Cell Surface; D049452:Green Fluorescent Proteins; D000068438:Brimonidine Tartrate; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: AGS3-Gαi Complex; Activator of G-protein Signaling 3; G-protein-coupled Receptors (GPCR); G-proteins; GPR Motif; Golgi; Secretory Pathway; Signal Transduction; Trafficking; trans-Golgi Network