The mechanism of MI arrest of starfish oocytes regulated by intracellular pH and MAP kinase

点击翻译按钮获取中文摘要

The mechanism of MI arrest in meiosis is poorly understood, although it is a widely observed phenomenon in invertebrates. The blockage of fully grown starfish oocytes in prophase of meiosis I is released by the hormone 1-methyladenine. It has been believed that meiosis of starfish oocytes proceeds completely without MI or MII arrest, even when fertilization dose not occur. In this study, we show that MI arrest of starfish oocytes occurs in the ovary after germinal vesicle breakdown. This arrest is maintained both by the Mos/MEK/MAP kinase pathway and the blockage of an increase of intracellular pH in the ovary before spawning. Immediately after spawning, an increase of intracellular pH (pHi) from〜7.0 to〜7.3 is induced by Na^+/H^+ antiporter in oocytes, and meiosis reinitiation occurs. An endogenous substrate of the proteasome, polyubiquitinated cyclin B, is stable at pH 7.0, while it is degraded at pH 7.3. When the MAP kinase pathway is blocked by MEK inhibitor U0126,degradation of polyubiquitinated cyclin B occurs even at pH 7.0 without an increase of the peptidase activity of the proteasome. These results indicate that the proteasome activity at pH 7.0 is sufficient for degradation of polyubiquitinated cyclin B and that the MAP kinase pathway blocks the degradation of polyubiquitinated cyclin B in the maturing oocytes in the ovary. Immediately after spawning, the increase in pHi mediated by Na^+/H^+ antiporter cancels the inhibitory effects of the MAP kinase pathway, resulting in the degradation of polyubiquitinated cyclin B and the release of the arrest. Thus, the key step of MI arrest in starfish oocytes occurs after the polyubiqutination of cyclin B but before cyclin B proteolysis by the proteasome.