PMID- 17989211
OWN - NLM
STAT- MEDLINE
DCOM- 20080221
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 294
IP  - 1
DP  - 2008 Jan
TI  - The role of VASP in regulation of cAMP- and Rac 1-mediated endothelial barrier 
      stabilization.
PG  - C178-88
AB  - 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.
FAU - Schlegel, N
AU  - Schlegel N
AD  - Institute of Anatomy and Cell Biology, University of Wurzburg, Wurzburg, Germany
FAU - Burger, S
AU  - Burger S
FAU - Golenhofen, N
AU  - Golenhofen N
FAU - Walter, U
AU  - Walter U
FAU - Drenckhahn, D
AU  - Drenckhahn D
FAU - Waschke, J
AU  - Waschke J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071107
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Antigens, CD)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Cadherins)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Cortactin)
RN  - 0 (Cttn protein, mouse)
RN  - 0 (Enzyme Activators)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Phosphoproteins)
RN  - 0 (Rac1 protein, mouse)
RN  - 0 (cadherin 5)
RN  - 0 (vasodilator-stimulated phosphoprotein)
RN  - 106803-33-2 (cytotoxic necrotizing factor type 1)
RN  - 1F7A44V6OU (Colforsin)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - K676NL63N7 (Rolipram)
SB  - IM
MH  - Adenylyl Cyclases/metabolism
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Bacterial Toxins/pharmacology
MH  - Cadherins/metabolism
MH  - *Capillary Permeability/drug effects
MH  - Cell Adhesion
MH  - Cell Adhesion Molecules/deficiency/genetics/*metabolism
MH  - Cell Line
MH  - Colforsin/pharmacology
MH  - Coronary Vessels/drug effects/enzymology/*metabolism
MH  - Cortactin/metabolism
MH  - Cyclic AMP/*metabolism
MH  - Endothelial Cells/drug effects/enzymology/*metabolism
MH  - Enzyme Activators/pharmacology
MH  - Escherichia coli Proteins/pharmacology
MH  - Intercellular Junctions/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Microfilament Proteins/deficiency/genetics/*metabolism
MH  - Neuropeptides/genetics/*metabolism
MH  - Phosphodiesterase Inhibitors/pharmacology
MH  - Phosphoproteins/deficiency/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Transport
MH  - Rolipram/pharmacology
MH  - *Signal Transduction/drug effects
MH  - Transfection
MH  - rac GTP-Binding Proteins/genetics/*metabolism
MH  - rac1 GTP-Binding Protein
EDAT- 2007/11/09 09:00
MHDA- 2008/02/22 09:00
CRDT- 2007/11/09 09:00
PHST- 2007/11/09 09:00 [pubmed]
PHST- 2008/02/22 09:00 [medline]
PHST- 2007/11/09 09:00 [entrez]
AID - 00273.2007 [pii]
AID - 10.1152/ajpcell.00273.2007 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2008 Jan;294(1):C178-88. doi: 
      10.1152/ajpcell.00273.2007. Epub 2007 Nov 7.