Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute of Technology (BIST), 08028 Barcelona, Spain.
Dev Cell. 2023 Sep 25;58(18):1748-1763.e6. doi: 10.1016/j.devcel.2023.06.011. Epub 2023 Jul 21.
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.
黏着连接（AJs）允许细胞接触来抑制上皮细胞迁移，同时也允许上皮细胞作为一个整体移动。那么，细胞如何识别哪些接触会抑制运动呢？在这里，我们表明，在人类上皮细胞中，这源于 AJs 处皮层流的方向。当来自不同迁移片层的先导细胞迎面相接时，它们组装 AJs，使相反方向的皮层流偶联。这对α-连环蛋白的肌动球蛋白结合域（ABD）施加了张力信号，从而提供了一个离合器，以促进侧向粘附生长并抑制迁移所需的片状伪足活性。相比之下，在同一迁移片层中的先导细胞之间发现的 AJs 具有相同方向的皮层流，并且不会发生这种机械抑制。因此，E-钙粘蛋白和皮层 F-肌动蛋白之间的离合器中α-连环蛋白的机械敏感性允许细胞通过皮层流来解释运动方向，并发出信号以抑制运动。
