G alpha s family G proteins activate IP3-Ca2+ signaling via G beta gamma and transduce ventralizing signals in Xenopus

During early embryonic development, IP3-Ca2+ signaling transduces ventral s ignaling at the time of dorsoventral axis formation. To identify molecules functioning upstream in this signal pathway, we examined effects of a panel of inhibitory antibodies against G alpha q/11, G alpha a/olf, or G alpha i /o/t/z. While all these antibodies showed direct inhibition of their target s, their effects on redirection of the ventral mesoderm to a dorsal fate va ried. Anti-G alpha s/olf antibody showed strong induction of dorsal fate, a nti-G alpha i/o/t/z antibody did so weakly, and anti-G alpha q/11 antibody was without effect. Injection of beta ARK, a G beta gamma inhibitor, mimick ed the dorsalizing effect of anti-G alpha s/olf antibody, whereas injection of adenylyl cyclase inhibitors at a concentration which inhibited G alpha s-coupled cAMP increase did not do so. The activation of G alpha s-coupled receptor gave rise to Ca2+ transients. All these results suggest that activ ation of the G alpha s-coupled receptor relays dorsoventral signal to G bet a gamma, which then stimulates PLC beta and then the IP3-Ca2+ system. This signaling pathway may play a crucial role in transducing ventral signals. ( C) 2000 Academic Press.