Institute of Physiology and Pathophysiology, Department of Molecular Cell Physiology, Philipps-University, Marburg, Germany.
Computer Graphics and Multimedia Programming, Philipps-University, Marburg, Germany.
Nat Commun. 2021 Feb 4;12(1):791. doi: 10.1038/s41467-020-20362-2.
Cells migrate collectively to form tissues and organs during morphogenesis. Contact inhibition of locomotion (CIL) drives collective migration by inhibiting lamellipodial protrusions at cell-cell contacts and promoting polarization at the leading edge. Here, we report a CIL-related collective cell behavior of myotubes that lack lamellipodial protrusions, but instead use filopodia to move as a cohesive cluster in a formin-dependent manner. We perform genetic, pharmacological and mechanical perturbation analyses to reveal the essential roles of Rac2, Cdc42 and Rho1 in myotube migration. These factors differentially control protrusion dynamics and cell-matrix adhesion formation. We also show that active Rho1 GTPase localizes at retracting free edge filopodia and that Rok-dependent actomyosin contractility does not mediate a contraction of protrusions at cell-cell contacts, but likely plays an important role in the constriction of supracellular actin cables. Based on these findings, we propose that contact-dependent asymmetry of cell-matrix adhesion drives directional movement, whereas contractile actin cables contribute to the integrity of the migrating cell cluster.
在形态发生过程中，细胞集体迁移以形成组织和器官。细胞运动接触抑制（CIL）通过抑制细胞-细胞接触处的片状伪足突起并促进前缘的极化来驱动集体迁移。在这里，我们报告了一种肌管的 CIL 相关集体细胞行为，这些肌管缺乏片状伪足，但以形式依赖的方式使用丝状伪足作为一个有凝聚力的簇移动。我们进行了遗传、药理学和机械扰动分析，以揭示 Rac2、Cdc42 和 Rho1 在肌管迁移中的重要作用。这些因素差异控制突起动力学和细胞-基质附着的形成。我们还表明，活性 Rho1 GTPase 定位于回缩的游离边缘丝状伪足，并且 Rok 依赖性肌动球蛋白收缩性并不介导细胞-细胞接触处突起的收缩，而是可能在细胞超微丝电缆的收缩中发挥重要作用。基于这些发现，我们提出，细胞-基质粘附的接触依赖性不对称性驱动定向运动，而收缩性肌动蛋白电缆有助于迁移细胞簇的完整性。
