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


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.

SUBMITTER: Noordstra I 

PROVIDER: S-EPMC7616453 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Noordstra Ivar I   Hermoso Mario Díez MD   Schimmel Lilian L   Bonfim-Melo Alexis A   Currin-Ross Denni D   Duong Cao Nguyen CN   Kalappurakkal Joseph Mathew JM   Morris Richard G RG   Vestweber Dietmar D   Mayor Satyajit S   Gordon Emma E   Roca-Cusachs Pere P   Yap Alpha S AS  

Developmental cell 20230721 18


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  ...[more]

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