Regulation of Xenopus oocyte meiosis arrest by G protein βγ subunits

Background: Progesterone induces the resumption of meiosis (maturation) in Xenopus oocytes through a nongenomic mechanism involving inhibition of an oocyte adenylyl cyclase and reduction of intracellular cAMP, However, progesterone action in Xenopus oocytes is not blocked by pertussis toxin, and this finding indicates that the inhibition of the oocyte adenylyl cyclase is not mediated by the or subunits of classical G(i)-type G proteins. Results: To investigate the possibility that G protein py subunits, rather than alpha subunits, play a key role in regulating oocyte maturation, we have employed two structurally distinct G protein beta gamma scavengers (G(t)alpha and beta ARK-C-CAAX) to sequester free G beta gamma dimers, We demonstrated that the injection of mRNA encoding either of these G beta gamma scavengers induced oocyte maturation. The G beta gamma scavengers bound an endogenous, membrane-associated G beta subunit, indistinguishable from Xenopus G beta1 derived from mRNA injection, The injection of Xenopus G beta1 mRNA, together with bovine G gamma2 mRNA, elevated oocyte cAMP levels and inhibited progesterone-induced oooyte maturation. Conclusion: An endogenous G protein beta gamma dimer, likely including Xenopus G beta1, is responsible for maintaining oocyte meiosis arrest. Resumption of meiosis is induced by G beta gamma scavengers in vitro or, naturally, by progesterone via a mechanism that suppresses the release of G beta gamma.