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Epac1 regulates integrity of endothelial cell junctions through VE‐cadherin
Author(s) -
Kooistra Matthijs R.H.,
Corada Monica,
Dejana Elisabetta,
Bos Johannes L.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.07.080
Subject(s) - microbiology and biotechnology , ve cadherin , rap1 , guanine nucleotide exchange factor , adherens junction , cytoskeleton , cadherin , actin cytoskeleton , umbilical vein , actin , chemistry , cell junction , endothelial stem cell , human umbilical vein endothelial cell , cell , biology , signal transduction , in vitro , biochemistry
We have previously shown that Rap1 as well as its guanine nucleotide exchange factor Epac1 increases cell–cell junction formation. Here, we show that activation of Epac1 with the exchange protein directly activated by cAMP (Epac)‐specific cAMP analog 8CPT‐2′O‐Me‐cAMP (007) resulted in a tightening of the junctions and a decrease in the permeability of the endothelial cell monolayer. In addition, 007 treatment resulted in the breakdown of actin stress fibers and the formation of cortical actin. These effects were completely inhibited by siRNA against Epac1. In VE‐cadherin knock‐out cells Epac1 did not affect cell permeability, whereas in cells re‐expressing VE‐cadherin this effect was restored. Finally, the effect of Epac activation on the actin cytoskeleton was independent of junction formation. From these results we conclude that in human umbilical vein endothelial cells Epac1 controls VE‐cadherin‐mediated cell junction formation and induces reorganization of the actin cytoskeleton.