School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
J Cell Sci. 2022 Mar 15;135(6). doi: 10.1242/jcs.259807. Epub 2022 Mar 23.
Formation of healthy mammalian eggs from oocytes requires specialised F-actin structures. F-actin disruption produces aneuploid eggs, which are a leading cause of human embryo deaths, genetic disorders and infertility. We found that oocytes contain prominent nuclear F-actin structures that are correlated with meiotic developmental capacity. We demonstrate that nuclear F-actin is a conserved feature of healthy mammalian oocytes and declines significantly with female reproductive ageing. Actin monomers used for nuclear F-actin assembly are sourced from an excess pool in the oocyte cytoplasm. Increasing monomeric G-actin transfer from the cytoplasm to the nucleus or directly enriching the nucleus with monomers led to assembly of stable nuclear F-actin bundles that significantly restrict chromatin mobility. By contrast, reducing G-actin monomer transfer by blocking nuclear import triggered assembly of a dense cytoplasmic F-actin network that is incompatible with healthy oocyte development. Overall, our data suggest that the large oocyte nucleus helps to maintain cytoplasmic F-actin organisation and that defects in this function are linked with reproductive age-related female infertility. This article has an associated First Person interview with Federica Giannini, joint first author of the paper.
从卵母细胞中形成健康的哺乳动物卵子需要专门的 F-肌动蛋白结构。F-肌动蛋白的破坏会产生非整倍体卵子，这是非整倍体卵子是人类胚胎死亡、遗传疾病和不孕的主要原因。我们发现卵母细胞中存在明显的核 F-肌动蛋白结构，这些结构与减数分裂发育能力相关。我们证明核 F-肌动蛋白是健康哺乳动物卵母细胞的一个保守特征，并且随着女性生殖年龄的增长而显著下降。用于核 F-肌动蛋白组装的肌动蛋白单体来源于卵母细胞质中的过剩池。增加单体 G-肌动蛋白从细胞质向核内的转移，或直接将单体富集到核内，会导致稳定的核 F-肌动蛋白束的组装，这显著限制了染色质的流动性。相比之下，通过阻止核内输入来减少 G-肌动蛋白单体的转移，会引发致密的细胞质 F-肌动蛋白网络的组装，这种网络与健康卵母细胞的发育不相容。总的来说，我们的数据表明，大的卵母细胞核有助于维持细胞质 F-肌动蛋白的组织，而这种功能的缺陷与生殖年龄相关的女性不孕有关。本文有一个相关的第一人称采访，受访者是该论文的共同第一作者 Federica Giannini。
