Chen Lu, Jiang Jun-Chao, Dai Xing-Xing, Fan Heng-Yu
Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
Sheng Li Xue Bao. 2020 Feb 25;72(1):48-62.
The mitogen-activated protein kinase (MAPK) signaling pathway is a highly conserved signal transduction pathway from yeast to human species, and is widely distributed in various eukaryotic cells. In almost all of the species studied over the past three decades, this signaling pathway plays a crucial role in the development of female germ cells and meiotic maturation. Especially in a variety of mammalian species including primates, rodents, and domestic animals, the MAPK signaling pathway is activated during the resumption of first oocyte meiosis and plays an indispensable role in meiotic spindle assembly and cell cycle progression. In granulosa cells of fully grown ovarian follicles, the MAPK pathway also mediates the physiological action of gonadotropins, including cumulus expansion, ovulation, and corpus luteum formation. Although the MAPK signaling pathway plays a wide range of physiological functions during the female reproduction process, and these functions are highly conserved in evolution, their underlying mechanisms, especially their direct and physiological target molecules, have not been sufficiently studied for a long time. In recent years, based on some new gene-editing mouse models and theoretical findings, as well as the wide application of various omics techniques, it has been further revealed that MAPK directly phosphorylates and activates the RNA binding protein cytoplasmic polyadenylation element-binding protein-1 (CPEB1), promoting poly(A) tail extension of maternal mRNA to regulate protein translation during meiotic recovery. These findings not only constitute the current basic mechanism of mammalian oocyte maturation and ovulation, but also provide useful research ideas for other related research in this field. In this review, we summarize the research findings in our laboratory and from other groups regarding the role of MAPK cascade in regulating oocyte maturation and ovulation. We also discuss the latest research progress on MAPK regulation of mRNA translation and degradation by directly activating the translation initiation complex and mRNA poly(A) polymerase by phosphorylation in the granulosa cells.
丝裂原活化蛋白激酶(MAPK)信号通路是一条从酵母到人类高度保守的信号转导通路,广泛分布于各种真核细胞中。在过去三十年研究的几乎所有物种中,该信号通路在雌性生殖细胞发育和减数分裂成熟过程中发挥着关键作用。特别是在包括灵长类动物、啮齿动物和家畜在内的多种哺乳动物物种中,MAPK信号通路在第一次卵母细胞减数分裂恢复过程中被激活,在减数分裂纺锤体组装和细胞周期进程中发挥不可或缺的作用。在完全成熟的卵泡颗粒细胞中,MAPK通路还介导促性腺激素的生理作用,包括卵丘扩展、排卵和黄体形成。尽管MAPK信号通路在雌性生殖过程中发挥着广泛的生理功能,且这些功能在进化过程中高度保守,但其潜在机制,尤其是其直接和生理靶分子,长期以来尚未得到充分研究。近年来,基于一些新的基因编辑小鼠模型和理论发现,以及各种组学技术的广泛应用,进一步揭示了MAPK直接磷酸化并激活RNA结合蛋白细胞质聚腺苷酸化元件结合蛋白1(CPEB1),促进母源mRNA的聚(A)尾延伸,以调控减数分裂恢复过程中的蛋白质翻译。这些发现不仅构成了哺乳动物卵母细胞成熟和排卵的当前基本机制,也为该领域的其他相关研究提供了有益的研究思路。在本综述中,我们总结了我们实验室以及其他团队关于MAPK级联在调控卵母细胞成熟和排卵中作用的研究发现。我们还讨论了MAPK通过在颗粒细胞中磷酸化直接激活翻译起始复合物和mRNA聚(A)聚合酶来调控mRNA翻译和降解的最新研究进展。