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

• Published in: Nature (London) 2000-12, Vol.408 (6813), p.723-727
• Main Authors: De Vries, Luc, Schiff, Max L, Snow, Bryan, Ortiz, Daniel F, Jordan, J. Dedrick, Brothers, Greg, Siderovski, David P, Diversé-Pierluissi, María
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biology; Calcium; Calcium - metabolism; Calcium channels; Calcium Channels, N-Type - metabolism; Cell physiology; Cells, Cultured; Chick Embryo; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Ganglia, Spinal - metabolism; Humanities and Social Sciences; Humans; letter; Molecular and cellular biology; Molecular Sequence Data; multidisciplinary; Neurons; Neurons - metabolism; Phosphorylation; Protein Structure, Tertiary; Protein-Tyrosine Kinases - metabolism; Proteins; Rats; Receptors, GABA-B - metabolism; Recombinant Fusion Proteins; RGS protein; RGS Proteins - genetics; RGS Proteins - metabolism; Science; Signal Transduction
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35047093

γ-Aminobutyric acid (GABA)B receptors couple to G o to inhibit N-type calcium channels in embryonic chick dorsal root ganglion neurons. The voltage-independent inhibition, mediated by means of a tyrosine-kinase pathway, 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. 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 effectors may represent an additional mechanism for signal termination in G-protein-coupled pathways.