Qian Weiyi, Yamaguchi Naoya, Lis Patrycja, Cammer Michael, Knaut Holger
Skirball Institute of Biomolecular Medicine and Department of Cell Biology, New York University Grossman School of Medicine, New York, United States.
These authors contributed equally to this work.
bioRxiv. 2023 Oct 5:2023.10.03.560679. doi: 10.1101/2023.10.03.560679.
In animals, cells often move as collectives to shape organs, close wounds, or-in the case of disease-metastasize. To accomplish this, cells need to generate force to propel themselves forward. The motility of singly migrating cells is driven largely by an interplay between Rho GTPase signaling and the actin network (Yamada and Sixt, 2019). Whether cells migrating as collectives use the same machinery for motility is unclear. Using the zebrafish posterior lateral line primordium as a model for collective cell migration, we find that active RhoA and myosin II cluster on the basal sides of the primordium cells and are required for primordium motility. Positive and negative feedbacks cause RhoA and myosin II activities to pulse. These pulses of RhoA signaling stimulate actin polymerization at the tip of the protrusions and myosin II-dependent actin flow and protrusion retraction at the base of the protrusions, and deform the basement membrane underneath the migrating primordium. This suggests that RhoA-induced actin flow on the basal sides of the cells constitutes the motor that pulls the primordium forward, a scenario that likely underlies collective migration in other-but not all (Bastock and Strutt, 2007; Lebreton and Casanova, 2013; Matthews et al., 2008)-contexts.
在动物体内，细胞常常集体移动以塑造器官、闭合伤口，或者在疾病情况下发生转移。为此，细胞需要产生力量来推动自身前进。单个迁移细胞的运动主要由Rho GTPase信号传导与肌动蛋白网络之间的相互作用驱动（山田和西克斯，2019年）。细胞集体迁移时是否使用相同的运动机制尚不清楚。我们以斑马鱼后侧线原基作为集体细胞迁移的模型，发现活性RhoA和肌球蛋白II聚集在原基细胞的基底侧，并且是原基运动所必需的。正反馈和负反馈导致RhoA和肌球蛋白II的活性产生脉冲。这些RhoA信号脉冲刺激突起尖端的肌动蛋白聚合以及突起基部的肌球蛋白II依赖性肌动蛋白流动和突起回缩，并使迁移的原基下方的基底膜变形。这表明细胞基底侧由RhoA诱导的肌动蛋白流动构成了拉动原基向前的动力，这种情况可能是其他（但不是所有，巴斯托克和斯特拉特，2007年；勒布雷顿和卡萨诺瓦，2013年；马修斯等人，2008年）情况下集体迁移的基础。
