Regulation of Xenopus oocyte meiosis arrest by G protein βγ subunits

Abstract

AbstractBackground: 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 α subunits of classical Gi-type G proteins.Results: To investigate the possibility that G protein βγ subunits, rather than α subunits, play a key role in regulating oocyte maturation, we have employed two structurally distinct G protein βγ scavengers (Gtα and βARK-CCAAX) to sequester free Gβγ dimers. We demonstrated that the injection of mRNA encoding either of these Gβγ scavengers induced oocyte maturation. The Gβγ scavengers bound an endogenous, membrane-associated Gβ subunit, indistinguishable from Xenopus Gβ1 derived from mRNA injection. The injection of Xenopus Gβ1 mRNA, together with bovine Gγ2 mRNA, elevated oocyte cAMP levels and inhibited progesterone-induced oocyte maturation.Conclusion: An endogenous G protein βγ dimer, likely including Xenopus Gβ1, is responsible for maintaining oocyte meiosis arrest. Resumption of meiosis is induced by Gβγ scavengers in vitro or, naturally, by progesterone via a mechanism that suppresses the release of Gβγ