Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20
Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20
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DOI：
10.1038/sj.emboj.7600953
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发表时间：
2006-02-22
期刊：
影响因子：
11.4
通讯作者：
Perry, ACF
中科院分区：
文献类型：
--
作者：
Shoji, S;Yoshida, N;Perry, ACF
可受精的哺乳动物卵母细胞在第二次减数分裂中期 (mII) 被细胞周期蛋白 B-Cdc2 异二聚体、成熟促进因子 (MPF) 阻滞。 MPF 通过一种未鉴定的细胞生长抑制因子 (CSF) 的活性来稳定，从而暂停减数分裂进程直至受精。我们在这里提出的证据表明，非洲爪蟾 XErp1/Emi2 的保守 71 kDa 哺乳动物直系同源物，我们称之为内源减数分裂抑制剂 2 (Emi2)，是 CSF 的重要组成部分。通过 RNA 干扰原位消除 Emi2 会引起成熟小鼠卵母细胞减数分裂提前退出。 Emi2 的减少使成熟的 mII 卵母细胞免于细胞抑制停滞，经常引起细胞变性。 mII 卵母细胞中 Mos 水平自主下降至不可检测的水平。重组 Emi2 降低了 mII 卵母细胞响应激活刺激而退出减数分裂的倾向。 Emi2 和 Cdc20 蛋白相互相互作用，Cdc20 消融消除了 Emi2 去除诱导中期释放的能力。与此一致的是，Cdc20 的去除阻止了孤雌生殖或精子诱导的减数分裂退出。这些研究表明，在完整的卵母细胞中，Emi2 与 Cdc20 的相互作用将激活刺激与哺乳动物受精时和孤雌生殖过程中减数分裂的恢复联系起来。
Fertilizable mammalian oocytes are arrested at the second meiotic metaphase ( mII) by the cyclinB- Cdc2 heterodimer, maturation promoting factor ( MPF). MPF is stabilized via the activity of an unidentified cytostatic factor ( CSF), thereby suspending meiotic progression until fertilization. We here present evidence that a conserved 71 kDa mammalian orthologue of Xenopus XErp1/ Emi2, which we term endogenous meiotic inhibitor 2 ( Emi2) is an essential CSF component. Depletion in situ of Emi2 by RNA interference elicited precocious meiotic exit in maturing mouse oocytes. Reduction of Emi2 released mature mII oocytes from cytostatic arrest, frequently inducing cytodegeneration. Mos levels autonomously declined to undetectable levels in mII oocytes. Recombinant Emi2 reduced the propensity of mII oocytes to exit meiosis in response to activating stimuli. Emi2 and Cdc20 proteins mutually interact and Cdc20 ablation negated the ability of Emi2 removal to induce metaphase release. Consistent with this, Cdc20 removal prevented parthenogenetic or sperm- induced meiotic exit. These studies show in intact oocytes that the interaction of Emi2 with Cdc20 links activating stimuli to meiotic resumption at fertilization and during parthenogenesis in mammals.