Protein Phosphatase 1 activity controls a balance between collective and single cell modes of migration
Protein Phosphatase 1 activity controls a balance between collective and single cell modes of migration
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DOI：
10.7554/elife.52979
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发表时间：
2020-05-05
期刊：
影响因子：
7.7
通讯作者：
Mcdonald, Jocelyn A.
中科院分区：
文献类型：
--
作者：
Chen, Yujun;Kotian, Nirupama;Mcdonald, Jocelyn A.
集体细胞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却知之甚少。使用果蝇边缘细胞迁移模型，我们发现蛋白磷酸酶1（Pp 1）的活性控制集体细胞的凝聚力和迁移。Pp 1的抑制导致边缘细胞聚集、解离并作为运动性改变的单细胞移动。我们目前的证据表明，Pp 1促进适当水平的钙粘蛋白-连环蛋白复合物蛋白在细胞连接簇内保持边界细胞在一起。PP 1进一步限制肌动球蛋白收缩集群周边，而不是在个别内部边界细胞接触。我们发现，肌球蛋白磷酸酶Pp 1复合物，抑制非肌肉肌球蛋白-II（肌球蛋白-II）的活动，协调边界细胞的形状和集群的凝聚力。鉴于Pp 1复合物的高度保守性，本研究将Pp 1确定为集体与单细胞迁移的主要调节因子。
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 Drosophila 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.