(Janos Bolyai Research Fellowship) Támogató: MTA Bolyai pályázat
(Start-up grant) Támogató: SE
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.
