Abstract:
Adherens junctions (AJs) allow cell contact to inhibit epithelial migration yet also permit epithelia to move as coherent sheets. How, then, do cells identify which contacts will inhibit locomotion? Here, we show that in human epithelial cells this arises from the orientation of cortical flows at AJs. When the leader cells from different migrating sheets make head-on contact with one another, they assemble AJs that couple together oppositely directed cortical flows. This applies a tensile signal to the actin-binding domain (ABD) of α-catenin, which provides a clutch to promote lateral adhesion growth and inhibit the lamellipodial activity necessary for migration. In contrast, AJs found between leader cells in the same migrating sheet have cortical flows aligned in the same direction, and no such mechanical inhibition takes place. Therefore, α-catenin mechanosensitivity in the clutch between E-cadherin and cortical F-actin allows cells to interpret the direction of motion via cortical flows and signal for contact to inhibit locomotion.
摘要:
粘附连接(AJ)允许细胞接触以抑制上皮迁移,但也允许上皮作为连贯的薄片移动。How,然后,细胞确定哪些接触会抑制运动吗?这里,我们表明,在人类上皮细胞中,这是由AJ处皮质流的方向引起的。当来自不同迁移工作表的前导单元彼此直接接触时,他们组装AJ,将相反方向的皮质流耦合在一起。这将拉伸信号施加到α-连环蛋白的肌动蛋白结合域(ABD),它提供了一种离合器,以促进侧向粘附生长并抑制迁移所需的层状体活性。相比之下,在同一迁移片中的前导细胞之间发现的AJ具有沿相同方向对齐的皮质流,并且不会发生这种机械抑制。因此,E-钙粘蛋白和皮质F-肌动蛋白之间的离合器中的α-catenin机械敏感性使细胞能够通过皮质流和接触信号来解释运动方向以抑制运动。