The GABA_Breceptor associates with regulators of G-protein signaling 4 protein in the mouse prefrontal cortex and hypothalamus

Abstract

Regulators of G-protein signaling (RGS) proteins regulate certain G-protein-coupled receptor (GPCR)-mediated signaling pathways. The GABAB receptor (GABABR) is a GPCR that plays a role in the stress response. Previous studies indicate that acute immobilization stress (AIS) decreases RGS4 in the prefrontal cortex (PFC) and hypothalamus (HY) and suggest the possibility of a signal complex composed of RGS4 and GABABR. Therefore, in the present study, we tested whether RGS4 associates with GABABR in these brain regions. We found the co-localization of RGS4 and GABABR subtypes in the PFC and HY using double immunohistochemistry and confirmed a direct association between GABAB2R and RGS4 proteins using co-immunoprecipitation. Furthermore, we found that AIS decreased the amount of RGS4 bound to GABAB2R and the number of double-positive cells. These results indicate that GABABR forms a signal complex with RGS4 and suggests that RGS4 is a regulator of GABABR. [BMB Reports 2014; 47(6): 324-329]

Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

“…RGS4-GFP was most abundant in the striatum and amygdala of the subcortex. In situ hybridization using RGS4 riboprobes revealed greater amounts of RGS4 in several regions of the frontal cortex with lower levels in the thalamus and striatum (Erdely et al, 2004;Ha et al, 2013;Heraud-Farlow et al, 2013;Kim et al, 2013;Lener et al, 2013;Li et al, 2013a;Steiner et al, 2014;Stratinaki et al, 2013;Wamsteeker Cusulin et al, 2013).…”

Mechanisms of Fast Desensitization of GABAB Receptor-Gated Currents

“…Additional experiments showed that RGS4 was responsible for enhancing the fast component of GABA B R-activated K + current desensitization in 293T cells. In keeping with these findings, RGS4 was later shown to associate with GABA B Rs (Kim et al, 2014), presumably as part of a complex that also includes the Kir3 channel and the G protein (Ciruela et al, 2010;David et al, 2006;Fowler, Aryal, Suen, & Slesinger, 2007) (Fig. 1A).…”

Effects of low doses of Tat-PIM2 protein against hippocampal neuronal cell survival

“…Immunohistochemistry was performed as described in previous studies [27,35]. The brain tissue samples were obtained at 7 days after ischemia-reperfusion.…”