SGK regulates pH increase and cyclin B-Cdk1 activation to resume meiosis in starfish ovarian oocytes

Abstract

AbstractTight regulation of intracellular pH (pHi) is essential for biological processes. Fully-grown oocytes, having a large nucleus called the germinal vesicle, arrest at meiotic prophase-I. Upon hormonal stimulus, oocytes resume meiosis to acquire fertilizability. At this time, pHi increases through Na+/H+ exchanger activity. However, regulation and function of this change remains obscure. Here we show that in starfish oocytes, serum- and glucocorticoid-regulated kinase (SGK) is activated by the PI3K/TORC2/PDK1 signaling after hormonal stimulus, and is required for the pHi increase and cyclin B–Cdk1 activation. Furthermore, when we clamped pHi at 6.7, corresponding to the pHi of unstimulated ovarian oocytes, hormonal stimulus normally induced cyclin B–Cdk1 activation; thereafter, oocytes initiated germinal vesicle breakdown (GVBD), but failed to complete it. Thus, SGK-dependent pHi increase is likely prerequisite for completion of GVBD in ovarian oocytes. We propose a model that SGK drives meiotic resumption through concomitant regulation of pHi and the cell-cycle machinery.