Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Elife. 2020 Jan 28;9:e49774. doi: 10.7554/eLife.49774.
The nucleus of oocytes (germinal vesicle) is unusually large and its nuclear envelope (NE) is densely packed with nuclear pore complexes (NPCs) that are stockpiled for embryonic development. We showed that breakdown of this specialized NE is mediated by an Arp2/3-nucleated F-actin 'shell' in starfish oocytes, in contrast to microtubule-driven tearing in mammalian fibroblasts. Here, we address the mechanism of F-actin-driven NE rupture by correlated live-cell, super-resolution and electron microscopy. We show that actin is nucleated within the lamina, sprouting filopodia-like spikes towards the nuclear membranes. These F-actin spikes protrude pore-free nuclear membranes, whereas the adjoining stretches of membrane accumulate NPCs that are associated with the still-intact lamina. Packed NPCs sort into a distinct membrane network, while breaks appear in ER-like, pore-free regions. We reveal a new function for actin-mediated membrane shaping in nuclear rupture that is likely to have implications in other contexts, such as nuclear rupture observed in cancer cells.
卵母细胞（生发泡）的核异常大，其核膜（NE）上紧密排列着核孔复合物（NPC），这些 NPC 为胚胎发育而储备。我们表明，海星卵母细胞中，由 Arp2/3 引发的 F-肌动蛋白“壳”介导了这种特化 NE 的破裂，而在哺乳动物成纤维细胞中则是微管驱动的撕裂。在这里，我们通过相关的活细胞、超分辨率和电子显微镜来解决 F-肌动蛋白驱动的 NE 破裂的机制。我们表明，肌动蛋白在层状结构内成核，向核膜延伸出类似于丝状伪足的刺。这些 F-肌动蛋白刺突出无孔的核膜，而相邻的膜段则积累与仍完整的层状结构相关联的 NPC。密集的 NPC 分类为一个独特的膜网络，而在 ER 样无孔区域则出现断裂。我们揭示了肌动蛋白介导的核破裂中膜重塑的新功能，这可能在其他情况下具有重要意义，例如在癌细胞中观察到的核破裂。
