An E-cadherin-actin clutch translates the mechanical force of cortical flow for cell-cell contact to inhibit epithelial cell locomotion

E-钙黏蛋白-肌动蛋白复合物将皮层流动产生的机械力转化为细胞间接触,从而抑制上皮细胞的运动。

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作者:Ivar Noordstra,Mario Díez Hermoso,Lilian Schimmel,Alexis Bonfim-Melo,Denni Currin-Ross,Cao Nguyen Duong,Joseph Mathew Kalappurakkal,Richard G Morris,Dietmar Vestweber,Satyajit Mayor,Emma Gordon,Pere Roca-Cusachs,Alpha S Yap

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.

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