皮质下母性复合物通过 14-3-3 调节早期哺乳动物胚胎发生过程中的细胞周期。

The subcortical maternal complex modulates the cell cycle during early mammalian embryogenesis via 14-3-3.

机构信息

Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.

State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Organ Regeneration and Reconstruction, UCAS/IOZ/CAS, Beijing, China.

出版信息

Nat Commun. 2024 Oct 15;15(1):8887. doi: 10.1038/s41467-024-53277-3.

DOI:10.1038/s41467-024-53277-3

PMID:39406751

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11480350/

Abstract

The subcortical maternal complex (SCMC) is essential for safeguarding female fertility in mammals. Assembled in oocytes, the SCMC maintains the cleavage of early embryos, but the underlying mechanism remains unclear. Here, we report that 14-3-3, a multifunctional protein, is a component of the SCMC. By resolving the structure of the 14-3-3-containing SCMC, we discover that phosphorylation of TLE6 contributes to the recruitment of 14-3-3. Mechanistically, during maternal-to-embryo transition, the SCMC stabilizes 14-3-3 protein and contributes to the proper control of CDC25B, thus ensuring the activation of the maturation-promoting factor and mitotic entry in mouse zygotes. Notably, the SCMC establishes a conserved molecular link with 14-3-3 and CDC25B in human oocytes/embryos. This study discloses the molecular mechanism through which the SCMC regulates the cell cycle in early embryos and elucidates the function of the SCMC in mammalian early embryogenesis.

摘要

皮质下母性复合物（SCMC）对于保障哺乳动物的雌性生育能力至关重要。SCMC 在卵母细胞中组装，维持早期胚胎的分裂，但潜在的机制尚不清楚。在这里，我们报告说多功能蛋白 14-3-3 是 SCMC 的一个组成部分。通过解析含有 14-3-3 的 SCMC 的结构，我们发现 TLE6 的磷酸化有助于 14-3-3 的募集。在母体到胚胎的转变过程中，机制上，SCMC 稳定了 14-3-3 蛋白，有助于适当控制 CDC25B，从而确保成熟促进因子的激活和有丝分裂进入小鼠受精卵。值得注意的是，SCMC 在人类卵母细胞/胚胎中与 14-3-3 和 CDC25B 建立了保守的分子联系。这项研究揭示了 SCMC 调节早期胚胎细胞周期的分子机制，并阐明了 SCMC 在哺乳动物早期胚胎发生中的功能。