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

Abstract

Tight 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.