Mapping of RGS12-Cav2.2 Channel Interaction

Analgesic α-Conotoxins Vc1.1 and Rg1A Inhibit N-Type Calcium Channels in Rat Sensory Neurons via GABABReceptor Activation

“…Our results suggest that the GPCR responsible is the GABA B receptor: first, Vc1.1 inhibition of N-type Ca al., 2007), Vc1.1 inhibition of N-type Ca 2ϩ currents in rat DRG neurons was antagonized when GTP was replaced in the patch pipette with GDP␤S, when the cells were incubated overnight with PTX, and when c-Src tyrosine kinase activity was inhibited. Activation of the GABA B receptor has been shown to inhibit N-type Ca 2ϩ channel current by voltage-dependent (relieved by a strong depolarizing prepulse) and voltage-independent pathways, and to be readily reversible after washout of baclofen (Richman and Diversé-Pierluissi, 2004;Raingo et al, 2007). No relief of Vc1.1 inhibition was observed after depolarizing prepulses to ϩ80 mV.…”

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

“…The PTB domain is involved in the recruitment of RGS12 in a phosphotyrosine-dependent manner to the SNARE-binding region of the Cav2.2 Ca 2þ channel (Richman et al, 2005), which is important for the rate of desensitization of GABAB receptor-mediated Ca 2þ current inhibition in DRG neurons (Richman and Diverse-Pierluissi, 2004;Schiff et al, 2000), and the PDZ has been shown to interact with a G-protein-coupled chemokine receptor, CXCR2, which facilitates its GAP action on CXCR2-mediated G-protein signals (Ishii and Kurachi, 2003). The GoLoco motif is a second Ga interaction site that binds specifically to GDP-bound Ga i subunits.…”

Role of regulator of G protein signaling proteins in bone

“…Several lines of evidences showed that cytosolic Ca 2+ oscillations are generated mainly by influx of extracellular Ca 2+ through multiple channels, which include L- and N-type channels, and Ca 2+ influx is necessary for maintenance of oscillations(123–126). Additionally RGS12 is capable of direct interaction with the N-type calcium channel through its PTB domain and modulates channel activity directly (123, 125, 126). Interestingly, by analyzing RGS12 gene expression pattern, we found that RGS12 is also prominently expressed in RANKL induced osteoclasts.…”