Center for Interdisciplinary Research in Biology, Collège de France, CNRS, INSERM, Université PSL, Paris, France.
Laboratoire Physico Chimie Curie, Institut Curie, CNRS, Université PSL, Paris, France.
Nat Commun. 2022 Aug 29;13(1):5070. doi: 10.1038/s41467-022-32675-5.
Cells remodel their cytoplasm with force-generating cytoskeletal motors. Their activity generates random forces that stir the cytoplasm, agitating and displacing membrane-bound organelles like the nucleus in somatic and germ cells. These forces are transmitted inside the nucleus, yet their consequences on liquid-like biomolecular condensates residing in the nucleus remain unexplored. Here, we probe experimentally and computationally diverse nuclear condensates, that include nuclear speckles, Cajal bodies, and nucleoli, during cytoplasmic remodeling of female germ cells named oocytes. We discover that growing mammalian oocytes deploy cytoplasmic forces to timely impose multiscale reorganization of nuclear condensates for the success of meiotic divisions. These cytoplasmic forces accelerate nuclear condensate collision-coalescence and molecular kinetics within condensates. Disrupting the forces decelerates nuclear condensate reorganization on both scales, which correlates with compromised condensate-associated mRNA processing and hindered oocyte divisions that drive female fertility. We establish that cytoplasmic forces can reorganize nuclear condensates in an evolutionary conserved fashion in insects. Our work implies that cells evolved a mechanism, based on cytoplasmic force tuning, to functionally regulate a broad range of nuclear condensates across scales. This finding opens new perspectives when studying condensate-associated pathologies like cancer, neurodegeneration and viral infections.
细胞利用产生力的细胞骨架马达重塑细胞质。它们的活动产生随机力，搅动细胞质，搅动和移位细胞膜结合的细胞器，如体细胞和生殖细胞中的核。这些力在核内传递，但它们对位于核内的类似液体的生物分子凝聚物的影响仍未被探索。在这里，我们在雌性生殖细胞卵母细胞的细胞质重塑过程中，通过实验和计算探测了不同的核凝聚物，包括核斑、Cajal 体和核仁。我们发现，不断生长的哺乳动物卵母细胞利用细胞质力来及时实现核凝聚物的多尺度重组，以成功进行减数分裂。这些细胞质力加速了核凝聚物内的碰撞-聚结和分子动力学。破坏这些力会减缓两个尺度上的核凝聚物重组，这与凝聚物相关的 mRNA 处理受损以及卵母细胞分裂受阻有关，而卵母细胞分裂是女性生育能力的关键。我们证实，细胞质力可以以进化上保守的方式在昆虫中重组核凝聚物。我们的工作表明，细胞基于细胞质力的调节进化出了一种机制，以在多个尺度上对广泛的核凝聚物进行功能调控。这一发现为研究与凝聚物相关的疾病（如癌症、神经退行性变和病毒感染）提供了新的视角。
