BRAF Modulates Stretch-Induced Intercellular Gap Formation through Localized Actin Reorganization

Hollósi, Anna and Pászty, Katalin and Kellermayer, Miklós and Charras, Guillaume and Varga, Andrea (2021) BRAF Modulates Stretch-Induced Intercellular Gap Formation through Localized Actin Reorganization. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (16). No. 8989. ISSN 1661-6596

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Abstract

Mechanical forces acting on cell-cell adhesion modulate the barrier function of endothelial cells. The actively remodeled actin cytoskeleton impinges on cell-cell adhesion to counteract external forces. We applied stress on endothelial monolayers by mechanical stretch to uncover the role of BRAF in the stress-induced response. Control cells responded to external forces by organizing and stabilizing actin cables in the stretched cell junctions. This was accompanied by an increase in intercellular gap formation, which was prevented in BRAF knockdown monolayers. In the absence of BRAF, there was excess stress fiber formation due to the enhanced reorganization of actin fibers. Our findings suggest that stretch-induced intercellular gap formation, leading to a decrease in barrier function of blood vessels, can be reverted by BRAF RNAi. This is important when the endothelium experiences changes in external stresses caused by high blood pressure, leading to edema, or by immune or cancer cells in inflammation or metastasis.

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