Receptor‐mediated translocation of AGS3 from the cell cortex to the Golgi Apparatus

Group II Activators of G‐protein signaling play diverse functional roles through their interaction with Gαi, Gαt and Gαo. We recently reported the regulation of the AGS3·Gαi signaling module by a cell surface, seven‐transmembrane receptor. Upon receptor activation, AGS3 reversibly dissociated from the cell cortex, but the trafficking of AGS3 and its regulation following receptor activation in this system is not known. We thus examined the subcellular distribution of AGS3 by immunofluorescence microscopy after receptor activation. In HEK cells and COS7 cells expressing the α 2A/D ‐AR, AGS3‐GFP and Gαi3, receptor activation resulted in the translocation of AGS3 from the cell cortex to a perinuclear region where it colocalized with the Golgi organelle marker GM130. The agonist‐induced translocation of AGS3 was reversed by the α 2A/D ‐AR antagonist rauwolscine (10 μM) and it was inhibited by the phospholipase C inhibitor U73122. AGS3 translocation was not observed in cells pretreated with pertussis toxin or Brefeldin A. The regulated oscillation of AGS3 between the cell cortex and the Golgi apparatus offers unexpected mechanisms for modulating protein secretion and Golgi dynamics.