The formation of ordered nanoclusters controls cadherin anchoring to actin and cell-cell contact fluidity

有序纳米团簇的形成控制钙粘蛋白锚定到肌动蛋白和细胞间接触流动性

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作者:Pierre-Olivier Strale, Laurence Duchesne, Grégoire Peyret, Lorraine Montel, Thao Nguyen, Evelyn Png, Robert Tampé, Sergey Troyanovsky, Sylvie Hénon, Benoit Ladoux, René-Marc Mège

Abstract

Oligomerization of cadherins could provide the stability to ensure tissue cohesion. Cadherins mediate cell-cell adhesion by forming trans-interactions. They form cis-interactions whose role could be essential to stabilize intercellular junctions by shifting cadherin clusters from a fluid to an ordered phase. However, no evidence has been provided so far for cadherin oligomerization in cellulo and for its impact on cell-cell contact stability. Visualizing single cadherins within cell membrane at a nanometric resolution, we show that E-cadherins arrange in ordered clusters, providing the first demonstration of the existence of oligomeric cadherins at cell-cell contacts. Studying the consequences of the disruption of the cis-interface, we show that it is not essential for adherens junction formation. Its disruption, however, increased the mobility of junctional E-cadherin. This destabilization strongly affected E-cadherin anchoring to actin and cell-cell rearrangement during collective cell migration, indicating that the formation of oligomeric clusters controls the anchoring of cadherin to actin and cell-cell contact fluidity.

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