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BRAF increases endothelial cell stiffness through reorganization of the actin cytoskeleton

Hollósi, Anna and Pászty, Katalin and Bunta, Bálint Levente and Bozó, Tamás and Kellermayer, Miklós and Debreczeni, Márta Lídia and Cervenak, László and Baccarini, Manuela and Varga, Andrea (2022) BRAF increases endothelial cell stiffness through reorganization of the actin cytoskeleton. FASEB JOURNAL, 36 (e22478). pp. 1-16. ISSN 0892-6638

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Abstract

The dynamics of the actin cytoskeleton and its connection to endothelial cell–cell junctions determine the barrier function of endothelial cells. The proper regulation of barrier opening/closing is necessary for the normal function of vessels, and its dysregulation can result in chronic and acute inflammation leading to edema formation. By using atomic force microscopy, we show here that thrombin-induced permeability of human umbilical vein endothelial cells, associated with actin stress fiber formation, stiffens the cell center. The depletion of the MEK/ERK kinase, BRAF reduces thrombin-induced permeability, prevents stress fiber formation and cell stiffening. The peripheral actin ring becomes stabilized by phosphorylated myosin light chain, while cofilin is excluded from the cell periphery. All these changes can be reverted by the inhibition of ROCK, but not of the MEK/ERK module. We propose that the balance between the binding of cofilin and myosin to F-actin in the cell periphery, which is regulated by the activity of ROCK, determines the local dynamics of actin reorganization, ultimately driving or preventing stress fiber formation.

Item Type: Article
Subjects: Q Science / természettudomány > Q1 Science (General) / természettudomány általában
Depositing User: Andrea Varga
Date Deposited: 03 Aug 2022 15:24
Last Modified: 03 Apr 2023 07:52
URI: http://real.mtak.hu/id/eprint/145683

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