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Publication

Interplay between Extracellular Matrix Stiffness and JAM-A Regulates Mechanical Load on ZO-1 and Tight Junction Assembly.

Cell reports | 2020

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.

Pubmed ID: 32697990 RIS Download

Research resources used in this publication

TS module (RRID:Addgene_26021) (plasmid)

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Associated grants

Agency: Medical Research Council, United Kingdom
Id: G0400678
Agency: Medical Research Council, United Kingdom
Id: G0900098
Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
Id: BB/N014855/1
Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
Id: BB/N001133/1

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