Division of Biology, Kansas State University, Manhattan, United States.
Lerner Research Institute, Cleveland Clinic, Cleveland, United States.
Elife. 2020 May 5;9:e52979. doi: 10.7554/eLife.52979.
Collective cell migration is central to many developmental and pathological processes. However, the mechanisms that keep cell collectives together and coordinate movement of multiple cells are poorly understood. Using the border cell migration model, we find that Protein phosphatase 1 (Pp1) activity controls collective cell cohesion and migration. Inhibition of Pp1 causes border cells to round up, dissociate, and move as single cells with altered motility. We present evidence that Pp1 promotes proper levels of cadherin-catenin complex proteins at cell-cell junctions within the cluster to keep border cells together. Pp1 further restricts actomyosin contractility to the cluster periphery rather than at individual internal border cell contacts. We show that the myosin phosphatase Pp1 complex, which inhibits non-muscle myosin-II (Myo-II) activity, coordinates border cell shape and cluster cohesion. Given the high conservation of Pp1 complexes, this study identifies Pp1 as a major regulator of collective versus single cell migration.
细胞集体迁移是许多发育和病理过程的核心。然而，保持细胞集体在一起并协调多个细胞运动的机制还了解甚少。使用边缘细胞迁移模型，我们发现蛋白磷酸酶 1（Pp1）活性控制着细胞集体的黏附和迁移。Pp1 的抑制会导致边缘细胞变圆、分离，并以单个细胞的形式移动，其运动性发生改变。我们提供的证据表明，Pp1 促进了细胞间连接中钙粘蛋白连环蛋白复合物蛋白的适当水平，以保持边缘细胞在一起。Pp1 进一步将肌球蛋白收缩力限制在集群的外围，而不是单个内部边缘细胞连接处。我们表明，肌球蛋白磷酸酶 Pp1 复合物抑制非肌球蛋白 II（Myo-II）的活性，协调了边缘细胞的形状和集群的黏合。鉴于 Pp1 复合物的高度保守性，本研究将 Pp1 确定为细胞集体迁移与单细胞迁移的主要调节因子。
