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

细胞内pH和MAP激酶调节海星卵母细胞心肌梗死的机制

基本信息

批准号：
15570171
负责人：
CHIBA Kazuyoshi
金额：
$ 2.37万
依托单位：
Ochanomizu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15570171/
关键词：
meiosis oocyte hormone pH starfish MAPK metaphase 第1減数分裂中期細胞内pH Na+H+アンチポーター

项目摘要

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.

虽然MI停滞在无脊椎动物中被广泛观察到，但对减数分裂中MI停滞的机制知之甚少。完全发育的海星卵母细胞在减数分裂前期的阻塞是由激素1-甲基腺嘌呤释放的。人们一直认为，海星卵母细胞的减数分裂完全进行，没有MI或MII停滞，即使没有受精发生。在这项研究中，我们发现海星卵母细胞的MI停滞发生在生发泡破裂后的卵巢。这种停滞是通过MOS/MEK/MAP激酶通路和阻断产卵前卵巢细胞内pH的升高来维持的。产卵后即刻，卵母细胞内Na~+/H~+逆向转运蛋白诱导胞内pH由~7.0升至~7.3，并重新启动减数分裂。蛋白酶体的内源底物多泛素化的周期蛋白B在pH 7.0时稳定，而在pH 7.3时被降解。当MAP激酶途径被MEK抑制剂U0126阻断时，即使在pH 7.0的情况下也能降解多泛素化的细胞周期蛋白B，而不会增加蛋白酶体的肽酶活性。这些结果表明，在卵巢成熟卵母细胞中，在pH为7.0时，蛋白酶体的活性足以降解多泛素化的细胞周期蛋白B，而MAP激酶途径阻止了多泛素化的细胞周期蛋白B的降解。产卵后，Na~(++)/H~(++)逆向转运体介导的pHi升高，抵消了MAP激酶途径的抑制作用，导致多泛素化的细胞周期蛋白B的降解和抑制作用的释放。因此，在海星卵母细胞中MI停滞的关键步骤发生在Cyclin B的多泛化之后，但在Cyclin B被蛋白酶体降解之前。

项目成果

期刊论文数量（36）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ca2+-promoted cyclin B1 degradation in mouse oocytes requires the establishment of a metaphase arrest

DOI：
10.1016/j.ydbio.2004.01.030
发表时间：
2004-05-01
期刊：
DEVELOPMENTAL BIOLOGY
影响因子：
2.7
作者：
Hyslop, LA;Nixon, VL;Jones, KT
通讯作者：
Jones, KT

Oita, E., Harada, K., Chiba, K.: "Degradation of polyubiquitinated cyclin B is blocked by the MAPK pathway at the Ml arrest in starfish oocytes."J.Biol.Chem.. (印刷中). (2004)

Oita, E.、Harada, K.、Chiba, K.：“海星卵母细胞 M1 停滞时，多泛素化细胞周期蛋白 B 的降解被 MAPK 途径阻断。”J.Biol.Chem..（出版中）。）

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Induction of apoptosis in starfish eggs requires spontaneous inactivation of MAPK(ERK) followed by activation of p38 MAPK.

海星卵细胞凋亡的诱导需要 MAPK(ERK) 自发失活，然后激活 p38 MAPK。

DOI：
发表时间：
2004
期刊：
Mol.Biol.Cell 15
影响因子：
0
作者：
Sasaki;K.;Chiba;K.
通讯作者：
K.

Hyslop, L.A., Nixon, V.L., Levasseur, M., Chapman, F., Chiba, K., McDougall, A., Venables, J.P., Elliott, D.J., Jones, K.T.: "Ca^<2+>-promoted cyclin B1 degradation in mouse oocytes requires the establishment of a metaphase arrest."Dev.Biol.. (印刷中). (2004

Hyslop, L.A.、Nixon, V.L.、Levasseur, M.、Chapman, F.、Chiba, K.、McDougall, A.、Venables, J.P.、Elliott, D.J.、Jones, K.T.：“Ca^<2+>-促进的细胞周期蛋白小鼠卵母细胞中的 B1 降解需要建立中期停滞。“Dev.Biol..（印刷中）。（2004 年）