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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-1-21
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pubmed:abstractText |
Regulation of actin dynamics is critical for endothelial barrier functions. We provide evidence that the actin-binding protein vasodilator-stimulated phosphoprotein (VASP) is required for endothelial barrier maintenance. Baseline permeability was significantly increased in VASP-deficient (VASP(-/-)) microvascular myocardial endothelial cells (MyEnd) in the absence of discernible alterations of immunostaining for adherens and tight junctions. We tested whether VASP is involved in the endothelium-stabilizing effects of cAMP or Rac 1. Forskolin and rolipram (F/R) to increase cAMP and cytotoxic necrotizing factor 1 (CNF-1) to activate Rac 1 were equally efficient to stabilize barrier functions in VASP(-/-) and wild-type (wt) cells. In wt cells, VASP was phosphorylated in response to F/R but did not localize to intercellular junctions. In contrast, CNF-1 and expression of constitutively active Rac 1 induced translocation of VASP to cell borders in wt cells, where it colocalized with active Rac 1. In VASP(-/-) cells, Rac 1 activity was reduced to 0.4 of wt levels in controls and increased approximately 20-fold in response to CNF-1 compared with 7-fold activation in wt cells. Moreover, inactivation of Rac 1 by lethal toxin led to a greater increase of permeability compared with wt cells. All these data suggest that VASP is involved in the regulation of Rac 1 activity. Taking these findings together, our study indicates that VASP at least in part stabilizes endothelial barrier functions by control of Rho-family GTPases.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Cortactin,
http://linkedlifedata.com/resource/pubmed/chemical/Cttn protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Escherichia coli Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Rac1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Rolipram,
http://linkedlifedata.com/resource/pubmed/chemical/cadherin 5,
http://linkedlifedata.com/resource/pubmed/chemical/cytotoxic necrotizing factor type 1,
http://linkedlifedata.com/resource/pubmed/chemical/rac GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/vasodilator-stimulated...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0363-6143
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
294
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C178-88
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pubmed:meshHeading |
pubmed-meshheading:17989211-Adenylate Cyclase,
pubmed-meshheading:17989211-Animals,
pubmed-meshheading:17989211-Antigens, CD,
pubmed-meshheading:17989211-Bacterial Toxins,
pubmed-meshheading:17989211-Cadherins,
pubmed-meshheading:17989211-Capillary Permeability,
pubmed-meshheading:17989211-Cell Adhesion,
pubmed-meshheading:17989211-Cell Adhesion Molecules,
pubmed-meshheading:17989211-Cell Line,
pubmed-meshheading:17989211-Coronary Vessels,
pubmed-meshheading:17989211-Cortactin,
pubmed-meshheading:17989211-Cyclic AMP,
pubmed-meshheading:17989211-Endothelial Cells,
pubmed-meshheading:17989211-Enzyme Activators,
pubmed-meshheading:17989211-Escherichia coli Proteins,
pubmed-meshheading:17989211-Forskolin,
pubmed-meshheading:17989211-Intercellular Junctions,
pubmed-meshheading:17989211-Mice,
pubmed-meshheading:17989211-Mice, Transgenic,
pubmed-meshheading:17989211-Microfilament Proteins,
pubmed-meshheading:17989211-Neuropeptides,
pubmed-meshheading:17989211-Phosphodiesterase Inhibitors,
pubmed-meshheading:17989211-Phosphoproteins,
pubmed-meshheading:17989211-Phosphorylation,
pubmed-meshheading:17989211-Protein Transport,
pubmed-meshheading:17989211-Rolipram,
pubmed-meshheading:17989211-Signal Transduction,
pubmed-meshheading:17989211-Transfection,
pubmed-meshheading:17989211-rac GTP-Binding Proteins
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pubmed:year |
2008
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pubmed:articleTitle |
The role of VASP in regulation of cAMP- and Rac 1-mediated endothelial barrier stabilization.
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pubmed:affiliation |
Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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