Epac1 regulates integrity of endothelial cell junctions through VE-cadherin
| Autor: | Johannes L. Bos, Matthijs R.H. Kooistra, Monica Corada, Elisabetta Dejana |
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| Rok vydání: | 2005 |
| Předmět: |
Biophysics
Biology Biochemistry Cell junction Adherens junction chemistry.chemical_compound Antigens CD Structural Biology cAMP Cyclic AMP Genetics Guanine Nucleotide Exchange Factors Humans RNA Small Interfering Cytoskeleton GTPase Molecular Biology Cells Cultured Actin Forskolin Endothelial Cells rap1 GTP-Binding Proteins Actin remodeling Cell Biology Cadherins Actin cytoskeleton Actins Cell biology Enzyme Activation Endothelial stem cell Intercellular Junctions chemistry RNAi Endothelium Vascular permeability |
| Zdroj: | FEBS Letters. 579:4966-4972 |
| ISSN: | 0014-5793 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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