Résumé
Tight-junction-regulated actomyosin activity determines epithelial and endothelial tension on adherens junctions and drives morphogenetic processes; however, whether or not tight junctions themselves are under tensile stress is not clear. Here, we use a tension sensor based on ZO-1, a scaffolding protein that links the junctional membrane to the cytoskeleton, to determine if tight junctions carry a mechanical load. Our data indicate that ZO-1 is under mechanical tension and that forces acting on ZO-1 are regulated by extracellular matrix (ECM) stiffness and the junctional adhesion molecule JAM-A. JAM-A depletion stimulates junctional recruitment of p114RhoGEF/ARHGEF18, mechanical tension on ZO-1, and traction forces at focal adhesions. p114RhoGEF is required for activation of junctional actomyosin activity and tight junction integrity on stiff but not soft ECM. Thus, junctional ZO-1 bears a mechanical load, and junction assembly is regulated by interplay between the physical properties of the ECM and adhesion-regulated signaling at tight junctions.
[Display omitted]
•Tight junctions and ZO-1 bear a mechanical load•ECM stiffness regulates mechanical tension on tight junctions and junction assembly•JAM-A regulates mechanical forces at tight junctions and focal adhesions•ECM-induced and junction-associated signaling cooperate to regulate junction assembly
Haas et al. reveal that mechanical forces acting on tight junctions are regulated by extracellular matrix properties and a cell-cell adhesion molecule. The adhesion protein regulates the activation of a junctional actomyosin regulatory mechanism that is required for tight junction assembly when forces acting on the junction are high.