Mori Masashi, Somogyi Kálmán, Kondo Hiroshi, Monnier Nilah, Falk Henning J, Machado Pedro, Bathe Mark, Nédélec François, Lénárt Péter
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, Heidelberg 69117, Germany.
Laboratory for Computational Biology and Biophysics, Department of Biological Engineering, Massachusetts Institute of Technology (MIT), 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Graduate Program in Biophysics, Harvard University, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA.
Curr Biol. 2014 Jun 16;24(12):1421-1428. doi: 10.1016/j.cub.2014.05.019. Epub 2014 Jun 5.
Animal cells disassemble and reassemble their nuclear envelopes (NEs) upon each division. Nuclear envelope breakdown (NEBD) serves as a major regulatory mechanism by which mixing of cytoplasmic and nuclear compartments drives the complete reorganization of cellular architecture, committing the cell for division. Breakdown is initiated by phosphorylation-driven partial disassembly of the nuclear pore complexes (NPCs), increasing their permeability but leaving the overall NE structure intact. Subsequently, the NE is rapidly broken into membrane fragments, defining the transition from prophase to prometaphase and resulting in complete mixing of cyto- and nucleoplasm. However, the mechanism underlying this rapid NE fragmentation remains largely unknown. Here, we show that NE fragmentation during NEBD in starfish oocytes is driven by an Arp2/3 complex-nucleated F-actin "shell" that transiently polymerizes on the inner surface of the NE. Blocking the formation of this F-actin shell prevents membrane fragmentation and delays entry of large cytoplasmic molecules into the nucleus. We observe spike-like protrusions extending from the F-actin shell that appear to "pierce" the NE during the fragmentation process. Finally, we show that NE fragmentation is essential for successful reproduction, because blocking this process in meiosis leads to formation of aneuploid eggs.
动物细胞在每次分裂时都会拆解并重新组装其核膜（NE）。核膜破裂（NEBD）是一种主要的调控机制，通过细胞质和细胞核区室的混合驱动细胞结构的完全重组，使细胞进入分裂状态。破裂由磷酸化驱动的核孔复合体（NPC）部分拆解引发，增加其通透性，但使整个核膜结构保持完整。随后，核膜迅速破碎成膜碎片，标志着从前期到前中期的转变，并导致细胞质和核质完全混合。然而，这种快速核膜破碎的潜在机制在很大程度上仍然未知。在这里，我们表明海星卵母细胞在核膜破裂期间的核膜破碎是由Arp2/3复合体成核的F-肌动蛋白“壳”驱动的，该“壳”在核膜内表面短暂聚合。阻止这种F-肌动蛋白壳的形成可防止膜破碎，并延迟大的细胞质分子进入细胞核。我们观察到从F-肌动蛋白壳延伸出的尖状突起，在破碎过程中似乎“刺穿”了核膜。最后，我们表明核膜破碎对于成功繁殖至关重要，因为在减数分裂中阻断这一过程会导致非整倍体卵子的形成。
