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

gamma -Aminobutyric acid (GABA)(B) receptors couple to G(o) to inhibit N-type calcium channels in embryonic chick dorsal root ganglion neurons(1). The voltage-independent inhibition, mediated by means of a tyrosine-kinase pathway(2), 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 RGS12 protein, in addition to the RGS domain, contains PDZ and PTB domains(3). Fusion proteins containing the PTB domain of RGS12 alter the rate of termination of the GABAB 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 protein capable of direct interactions through its PTB domain with the tyrosine-phosphorylated calcium channel. Recruitment of RGS proteins to G-protein effecters may represent an additional mechanism for signal termination in G-protein-coupled pathways.