Selective coupling of G protein beta gamma complexes to inhibition of Ca2+channels

Several mechanisms couple heterotrimeric guanine nucleotide-binding protein s (G proteins) to cellular effecters. Although alpha subunits of G proteins (G alpha) were the first recognized mediators of receptor-effector couplin g, G beta gamma regulation of effecters is now well known. Five G beta and 12 G gamma subunit genes have been identified, suggesting through their div ersity that specific subunits couple selectively to effecters. The molecula r determinants of G beta gamma-effector coupling, however, are not well und erstood, and most studies of G protein-effector coupling do not support sel ectivity of G beta gamma action. To explore this issue further, we have int roduced recombinant G beta gamma complexes into avian sensory neurons and m easured the inhibition of Ca2+ currents mediated by an endogenous phospholi pase C beta- (PLC beta) and protein kinase C-dependent pathway. Activities of G beta gamma in the native cells were compared with enzyme assays perfor med in vitro. We report a surprising selective activation of the PLC beta p athway by G beta gamma complexes containing beta(1) subunits, whereas beta( 2)-containing complexes produced no activation. In contrast, when assayed i n vitro, PLC beta and type II adenylyl cyclase did not discriminate among t hese same G beta gamma complexes, suggesting the possibility that additiona l cellular determinants confer specificity in vivo.