Accurate centrosome separation and positioning during early mitosis relies on force-generating mechanisms regulated by a combination of extracellular, cytoplasmic, and nuclear cues. The identity of the nuclear cues involved in this process remains largely unknown. Here, we investigate how the prophase nucleus contributes to centrosome positioning during the initial stages of mitosis, using a combination of cell micropatterning, high-resolution live-cell imaging, and quantitative 3D cellular reconstruction. We show that in untransformed RPE-1 cells, centrosome positioning is regulated by a nuclear signal, independently of external cues. This nuclear mechanism relies on the linker of nucleoskeleton and cytoskeleton complex that controls the timely loading of dynein on the nuclear envelope (NE), providing spatial cues for robust centrosome positioning on the shortest nuclear axis, before nuclear envelope permeabilization. Our results demonstrate how nuclear-cytoskeletal coupling maintains a robust centrosome positioning mechanism to ensure efficient mitotic spindle assembly.

中文翻译：

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LINC 复合物确保了前期中心体的准确定位。

早期有丝分裂过程中中心体的准确分离和定位依赖于由细胞外、细胞质和核信号组合调节的力产生机制。这一过程中涉及的核线索的身份在很大程度上仍然未知。在这里，我们结合使用细胞微图案、高分辨率活细胞成像和定量 3D 细胞重建，研究前期细胞核如何在有丝分裂的初始阶段对中心体定位做出贡献。我们发现，在未转化的 RPE-1 细胞中，中心体定位受核信号调节，独立于外部信号。这种核机制依赖于核骨架和细胞骨架复合物的连接体，控制动力蛋白在核膜（NE）上的及时加载，为核膜透化之前在最短核轴上的稳健中心体定位提供空间线索。我们的结果证明了核-细胞骨架耦合如何维持强大的中心体定位机制，以确保有效的有丝分裂纺锤体组装。