eprintid: 10133768 rev_number: 14 eprint_status: archive userid: 608 dir: disk0/10/13/37/68 datestamp: 2021-09-02 10:35:10 lastmod: 2021-09-24 21:55:39 status_changed: 2021-09-02 10:35:10 type: article metadata_visibility: show creators_name: Hollósi, A creators_name: Pászty, K creators_name: Kellermayer, M creators_name: Charras, G creators_name: Varga, A title: BRAF Modulates Stretch-Induced Intercellular Gap Formation through Localized Actin Reorganization ispublished: pub divisions: UCL divisions: B04 divisions: C06 divisions: F64 keywords: actin cytoskeleton; BRAF RNAi; endothelial monolayer; intercellular gaps; mechanical stretch note: This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited 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. date: 2021-08-02 date_type: published official_url: https://doi.org/10.3390/ijms22168989 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1883893 doi: 10.3390/ijms22168989 lyricists_name: Charras, Guillaume lyricists_id: GCHAR39 actors_name: Barczynska, Patrycja actors_id: PBARC91 actors_role: owner full_text_status: public publication: International Journal of Molecular Sciences volume: 22 number: 16 article_number: 8989 citation: Hollósi, A; Pászty, K; Kellermayer, M; Charras, G; Varga, A; (2021) BRAF Modulates Stretch-Induced Intercellular Gap Formation through Localized Actin Reorganization. International Journal of Molecular Sciences , 22 (16) , Article 8989. 10.3390/ijms22168989 <https://doi.org/10.3390/ijms22168989>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10133768/1/ijms-22-08989-v2.pdf