Institute of Pharmacology, University of Freiburg, Freiburg, Germany.
Department of Systems and Synthetic Microbiology, Max Planck Institute for Terrestrial Microbiology and LOEWE Center for Synthetic Microbiology (SYNMIKRO), Marburg, Germany.
EMBO Rep. 2020 Nov 5;21(11):e50758. doi: 10.15252/embr.202050758. Epub 2020 Sep 22.
The actin cytoskeleton operates in a multitude of cellular processes including cell shape and migration, mechanoregulation, and membrane or organelle dynamics. However, its filamentous properties and functions inside the mammalian cell nucleus are less well explored. We previously described transient actin assembly at mitotic exit that promotes nuclear expansion during chromatin decondensation. Here, we identify non-muscle α-actinin 4 (ACTN4) as a critical regulator to facilitate F-actin reorganization and bundling during postmitotic nuclear expansion. ACTN4 binds to nuclear actin filament structures, and ACTN4 clusters associate with nuclear F-actin in a highly dynamic fashion. ACTN4 but not ACTN1 is required for proper postmitotic nuclear volume expansion, mediated by its actin-binding domain. Using super-resolution imaging to quantify actin filament numbers and widths in individual nuclei, we find that ACTN4 is necessary for postmitotic nuclear actin reorganization and actin filament bundling. Our findings uncover a nuclear cytoskeletal function for ACTN4 to control nuclear size and chromatin organization during mitotic cell division.
肌动蛋白细胞骨架在多种细胞过程中发挥作用，包括细胞形状和迁移、机械调节以及膜或细胞器的动态变化。然而，其在哺乳动物细胞核内的丝状特性和功能还不太为人所知。我们之前描述了有丝分裂末期短暂的肌动蛋白组装，该组装在染色质去浓缩过程中促进核扩张。在这里，我们确定非肌肉α-辅肌动蛋白 4（ACTN4）是一个关键调节因子，可促进有丝分裂后核扩张过程中 F-肌动蛋白的重组和束集。ACTN4 结合到核肌动蛋白丝结构上，ACTN4 簇以高度动态的方式与核 F-肌动蛋白相关联。ACTN4 而不是 ACTN1 对于适当的有丝分裂后核体积扩张是必需的，这是由其肌动蛋白结合结构域介导的。使用超分辨率成像来量化单个核内肌动蛋白丝的数量和宽度，我们发现 ACTN4 对于有丝分裂后核肌动蛋白的重组和肌动蛋白丝的束集是必需的。我们的发现揭示了 ACTN4 在有丝分裂细胞分裂过程中控制核大小和染色质组织的核细胞骨架功能。
