BRAF Modulates Stretch-Induced Intercellular Gap Formation through Localized Actin Reorganization |
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| Authors: | Anna Hollsi Katalin Pszty Mikls Kellermayer Guillaume Charras Andrea Varga |
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| Affiliation: | 1.Department of Biophysics and Radiation Biology, Semmelweis University, H-1094 Budapest, Hungary; (A.H.); (K.P.); (M.K.);2.London Centre for Nanotechnology, University College London, London WC1H 0AH, UK;3.Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK |
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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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| Keywords: | actin cytoskeleton BRAF RNAi endothelial monolayer intercellular gaps mechanical stretch |
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