Kim Dong-Hwee, Cho Sangkyun, Wirtz Denis
Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
J Cell Sci. 2014 Jun 1;127(Pt 11):2528-41. doi: 10.1242/jcs.144345. Epub 2014 Mar 17.
Although eukaryotic cells are known to alternate between 'advancing' episodes of fast and persistent movement and 'hesitation' episodes of low speed and low persistence, the molecular mechanism that controls the dynamic changes in morphology, speed and persistence of eukaryotic migratory cells remains unclear. Here, we show that the movement of the interphase nucleus during random cell migration switches intermittently between two distinct modes - rotation and translocation - that follow with high fidelity the sequential rounded and elongated morphologies of the nucleus and cell body, respectively. Nuclear rotation and translocation mediate the stop-and-go motion of the cell through the dynamic formation and dissolution, respectively, of the contractile perinuclear actin cap, which is dynamically coupled to the nuclear lamina and the nuclear envelope through LINC complexes. A persistent cell movement and nuclear translocation driven by the actin cap are halted following the disruption of the actin cap, which in turn allows the cell to repolarize for its next persistent move owing to nuclear rotation mediated by cytoplasmic dynein light intermediate chain 2.
尽管已知真核细胞在快速持续运动的“推进”阶段和低速低持续性的“犹豫”阶段之间交替，但控制真核迁移细胞形态、速度和持续性动态变化的分子机制仍不清楚。在这里，我们表明，在随机细胞迁移过程中，间期细胞核的运动在两种不同模式之间间歇性切换——旋转和平移——分别与细胞核和细胞体依次出现的圆形和伸长形态高度一致。核旋转和平移分别通过收缩性核周肌动蛋白帽的动态形成和解聚介导细胞的走走停停运动，该肌动蛋白帽通过LINC复合体与核纤层和核膜动态耦合。肌动蛋白帽驱动的持续细胞运动和核平移在肌动蛋白帽被破坏后停止，这反过来又使细胞能够重新极化，以便由于细胞质动力蛋白轻中间链2介导的核旋转而进行下一次持续移动。
