Galphas family G proteins activate IP(3)-Ca(2+) signaling via gbetagamma and transduce ventralizing signals in Xenopus.
During early embryonic development, IP(3)-Ca(2+) signaling transduces ventral signaling 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 Galphaq/11, Galphas/olf, or Galphai/o/t/z. While all these antibodies showed direct inhibition of their targets, their effects on redirection of the ventral mesoderm to a dorsal fate varied. Anti-Galphas/olf antibody showed strong induction of dorsal fate, anti-Galphai/o/t/z antibody did so weakly, and anti-Galphaq/11 antibody was without effect. Injection of betaARK, a Gbetagamma inhibitor, mimicked the dorsalizing effect of anti-Galphas/olf antibody, whereas injection of adenylyl cyclase inhibitors at a concentration which inhibited Galphas-coupled cAMP increase did not do so. The activation of Galphas-coupled receptor gave rise to Ca(2+) transients. All these results suggest that activation of the Galphas-coupled receptor relays dorsoventral signal to Gbetagamma, which then stimulates PLCbeta and then the IP(3)-Ca(2+) system. This signaling pathway may play a crucial role in transducing ventral signals.
Kume
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Mikoshiba Calciosignal Net Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, 2-28-8 Honkomagome, Bunkyo-ku, Tokyo, 113-0021, Japan.
Inoue
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Mikoshiba
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K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008969:Molecular Sequence Data; D015398:Signal Transduction; D014981:Xenopus
D017931:DNA Primers; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D002118:Calcium