Selective coupling of G protein beta gamma complexes to inhibition of Ca2+ channels.
Several mechanisms couple heterotrimeric guanine nucleotide-binding proteins (G proteins) to cellular effectors. Although alpha subunits of G proteins (Galpha) were the first recognized mediators of receptor-effector coupling, Gbetagamma regulation of effectors is now well known. Five Gbeta and 12 Ggamma subunit genes have been identified, suggesting through their diversity that specific subunits couple selectively to effectors. The molecular determinants of Gbetagamma-effector coupling, however, are not well understood, and most studies of G protein-effector coupling do not support selectivity of Gbetagamma action. To explore this issue further, we have introduced recombinant Gbetagamma complexes into avian sensory neurons and measured the inhibition of Ca(2+) currents mediated by an endogenous phospholipase Cbeta- (PLCbeta) and protein kinase C-dependent pathway. Activities of Gbetagamma in the native cells were compared with enzyme assays performed in vitro. We report a surprising selective activation of the PLCbeta pathway by Gbetagamma complexes containing beta(1) subunits, whereas beta(2)-containing complexes produced no activation. In contrast, when assayed in vitro, PLCbeta and type II adenylyl cyclase did not discriminate among these same Gbetagamma complexes, suggesting the possibility that additional cellular determinants confer specificity in vivo.
Diversé-Pierluissi
M
M
Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
McIntire
W E
WE
Myung
C S
CS
Lindorfer
M A
MA
Garrison
J C
JC
Goy
M F
MF
Dunlap
K
K
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D002642:Chick Embryo; D019204:GTP-Binding Proteins / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D010738:Type C Phospholipases / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011994:Recombinant Proteins; D011493:Protein Kinase C; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins