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

Background:The AGS3⅐G␣ i complex is regulated by a GPCR, but downstream signaling events are unknown. Results: Upon receptor activation, AGS3 translocates to the Golgi apparatus, where it regulates events at the TGN. Conclusion: The AGS3⅐G␣ i complex serves as a signal transducer for GPCRs. Significance: The regulated translocation of AGS3 offers unexpected mechanisms for modulating protein secretion and/or endosome recycling events at the TGN.

Activator of G-Protein Signaling 3–Induced Lysosomal Biogenesis Limits Macrophage Intracellular Bacterial Infection

“…AGS3-induced changes in the trans -Golgi network could also promote endosome/lysosome enrichment. AGS3 can translocate to the trans -Golgi network (20), which leads to its fragmentation/vesiculation (19). Since the trans -Golgi network serves as a critical hub for the trafficking of resident lysosome proteins, high levels of AGS3 may enhance endosome and/or lysosome formation via this mechanism (32).…”

“…As a GDI, AGS3 binds to the Gi/Go/transducin family of G proteins via its G-protein regulatory (GPR/GoLoco) motif and stabilizes the Gα subunit in its GDP-bound conformation. AGS3 has been implicated in a surprisingly broad array of intracellular functions including neuronal asymmetric cell divisions (9), adaptive responses to addiction and craving behavior (10–13), autophagy (14–18), membrane protein trafficking (19, 20), metabolism, cardiovascular function (21), polycystic kidney disease (22–24), and leukocyte migration (25–27). In macrophages, LPS stimulation raised AGS3 levels, which led to lysosomal enrichment and a decreased susceptibility to three different antibiotic resistant bacteria.…”

Activators of G Protein Signaling Exhibit Broad Functionality and Define a Distinct Core Signaling Triad

“…Activation of the a 2 -AR leads to dissociation of the GaAGS3 and the GaAGS4 complex and release of the GPR protein from the inner face of the plasma membrane (Oner et al, 2010a(Oner et al, ,b, 2013b. Both transfected and endogenous AGS3 translocate to the Golgi apparatus subsequent to dissociation from Ga (Oner et al, 2013b).…”

“…2A), function as part of a distinct signaling pathway (e.g., GaGPR signaling module) (Fig. 2B), serve as a chaperone for Ga, and/or impact basic cellular events such as autophagy (Pattingre et al, 2003;Groves et al, 2010;Vural et al, 2010;Garcia-Marcos et al, 2011a) and secretory pathway dynamics (Groves et al, 2007;Oner et al, 2013b).…”

Activators of G Protein Signaling in the Kidney

“…Gbg activity has been implicated in mitotic spindle orientation (Sanada and Tsai, 2005), ion channel activity (Kwon et al, 2012), cAMP production (Fan et al, 2009), or modulation of GPCR-dependent Oner et al, 2010Oner et al, , 2013 and GPCR-independent signaling pathways (Smrcka, 2008;Smrcka et al, 2008;Lin and Smrcka, 2011). Overexpression of AGS3/GPSM1 facilitated an increase of polycystin-1/-2 ion channel activity, which could be blocked by a scavenger of Gbg dimers (Kwon et al, 2012).…”