Tyrosine-kinase-dependent recruitment of RGS12 to the N-type calcium channel

γ-Aminobutyric acid (GABA)_B receptors couple to G_o to inhibit N-type calcium channels in embryonic chick dorsal toot ganglion neurons¹. The voltage-independent inhibition, mediated by means of a tyrosine-kinase pathway², is transient and lasts up to 100 seconds. Inhibition of endogenous RGS12, a member of the family of regulators of G-protein signalling, selectively alters the time course of voltage-independent inhibition. The RGSI2 protein, in addition to the RGS domain, contains PDZ and PTB domains³. Fusion proteins containing the PTB domain of RGS12 alter the rate of termination of the GABA_B signal, whereas the PDZ or RGS domains of RGS12 have no observable effects. Using primary dorsal root ganglion neurons in culture, here we show an endogenous agonist-induced tyrosine-kinase-dependent complex of RGS12 and the calcium channel. These results indicate that RGS12 is a multifunctional protien capable of direct interactions through its PTB domain with the tyrosine-phosporylated calcium channel. Recruitment of RGS protiens to G-protien effectors may represent an additional mechanism for signal termination in G-protien effectors may represent an additional mechanism for signal termination in G-protien-coupled pathways.