BRAF increases endothelial cell stiffness through reorganization of the actin cytoskeleton

Autor(en)

Anna Hollósi, Katalin Pászty, Bálint Levente Bunta, Tamás Bozó, Miklós Kellermayer, Márta Lídia Debreczeni, László Cervenak, Manuela Baccarini, Andrea Varga

Abstrakt

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.

Organisation(en)

Department für Mikrobiologie, Immunbiologie und Genetik

Externe Organisation(en)

Semmelweis University

Journal

The FASEB Journal

Band

36

ISSN

0892-6638

DOI

https://doi.org/10.1096/fj.202200344R

Publikationsdatum

09-2022

Peer-reviewed

Ja

ÖFOS 2012

106023 Molekularbiologie, 106052 Zellbiologie

Schlagwörter

ASJC Scopus Sachgebiete

Genetics, Molecular Biology, Biochemistry, Biotechnology

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/5aa92619-ec67-4124-a79f-9a77431919e4