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RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system

Raf Ponsaerts, Catheleyne D'Hondt, Fréderic Hertens, Jan B Parys, Luc Leybaert UGent, Johan Vereecke, Bernard Himpens and Geert Bultynck (2012) PLOS ONE. 7(7).
abstract
ATP-dependent paracrine signaling, mediated via the release of ATP through plasma membrane-embedded hemichannels of the connexin family, coordinates a synchronized response between neighboring cells. Connexin 43 (Cx43) hemichannels that are present in the plasma membrane need to be tightly regulated to ensure cell viability. In monolayers of bovine corneal endothelial cells (BCEC),Cx43-mediated ATP release is strongly inhibited when the cells are treated with inflammatory mediators, in particular thrombin and histamine. In this study we investigated the involvement of RhoA activation in the inhibition of hemichannel-mediated ATP release in BCEC. We found that RhoA activation occurs rapidly and transiently upon thrombin treatment of BCEC. The RhoA activity correlated with the onset of actomyosin contractility that is involved in the inhibition of Cx43 hemichannels. RhoA activation and inhibition of Cx43-hemichannel activity were both prevented by pre-treatment of the cells with C3-toxin as well as knock down of RhoA by siRNA. These findings provide evidence that RhoA activation is a key player in thrombin-induced inhibition of Cx43-hemichannel activity. This study demonstrates that RhoA GTPase activity is involved in the acute inhibition of ATP-dependent paracrine signaling, mediated by Cx43 hemichannels, in response to the inflammatory mediator thrombin. Therefore, RhoA appears to be an important molecular switch that controls Cx43 hemichannel openings and hemichannel-mediated ATP-dependent paracrine intercellular communication under (patho) physiological conditions of stress.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
INTERCELLULAR CALCIUM WAVE, CORNEAL ENDOTHELIAL-CELLS, THROMBIN-INDUCED INHIBITION, GAP-JUNCTION CHANNELS, ATP RELEASE, MYOSIN-II, MEMBRANE PERMEABILIZATION, CONNEXIN HEMICHANNELS, ASTROCYTOMA-CELLS, COMMUNICATION
journal title
PLOS ONE
PLoS One
volume
7
issue
7
article_number
e42074
pages
10 pages
Web of Science type
Article
Web of Science id
000306950900064
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
3.73 (2012)
JCR rank
7/56 (2012)
JCR quartile
1 (2012)
ISSN
1932-6203
DOI
10.1371/journal.pone.0042074
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
3050579
handle
http://hdl.handle.net/1854/LU-3050579
date created
2012-11-09 21:12:41
date last changed
2012-11-12 10:44:50
@article{3050579,
  abstract     = {ATP-dependent paracrine signaling, mediated via the release of ATP through plasma membrane-embedded hemichannels of the connexin family, coordinates a synchronized response between neighboring cells. Connexin 43 (Cx43) hemichannels that are present in the plasma membrane need to be tightly regulated to ensure cell viability. In monolayers of bovine corneal endothelial cells (BCEC),Cx43-mediated ATP release is strongly inhibited when the cells are treated with inflammatory mediators, in particular thrombin and histamine. In this study we investigated the involvement of RhoA activation in the inhibition of hemichannel-mediated ATP release in BCEC. We found that RhoA activation occurs rapidly and transiently upon thrombin treatment of BCEC. The RhoA activity correlated with the onset of actomyosin contractility that is involved in the inhibition of Cx43 hemichannels. RhoA activation and inhibition of Cx43-hemichannel activity were both prevented by pre-treatment of the cells with C3-toxin as well as knock down of RhoA by siRNA. These findings provide evidence that RhoA activation is a key player in thrombin-induced inhibition of Cx43-hemichannel activity. This study demonstrates that RhoA GTPase activity is involved in the acute inhibition of ATP-dependent paracrine signaling, mediated by Cx43 hemichannels, in response to the inflammatory mediator thrombin. Therefore, RhoA appears to be an important molecular switch that controls Cx43 hemichannel openings and hemichannel-mediated ATP-dependent paracrine intercellular communication under (patho) physiological conditions of stress.},
  articleno    = {e42074},
  author       = {Ponsaerts, Raf and D'Hondt, Catheleyne and Hertens, Fr{\'e}deric and Parys, Jan B and Leybaert, Luc and Vereecke, Johan and Himpens, Bernard and Bultynck, Geert},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {INTERCELLULAR CALCIUM WAVE,CORNEAL ENDOTHELIAL-CELLS,THROMBIN-INDUCED INHIBITION,GAP-JUNCTION CHANNELS,ATP RELEASE,MYOSIN-II,MEMBRANE PERMEABILIZATION,CONNEXIN HEMICHANNELS,ASTROCYTOMA-CELLS,COMMUNICATION},
  language     = {eng},
  number       = {7},
  pages        = {10},
  title        = {RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system},
  url          = {http://dx.doi.org/10.1371/journal.pone.0042074},
  volume       = {7},
  year         = {2012},
}

Chicago
Ponsaerts, Raf, Catheleyne D’Hondt, Fréderic Hertens, Jan B Parys, Luc Leybaert, Johan Vereecke, Bernard Himpens, and Geert Bultynck. 2012. “RhoA GTPase Switch Controls Cx43-hemichannel Activity Through the Contractile System.” Plos One 7 (7).
APA
Ponsaerts, R., D’Hondt, C., Hertens, F., Parys, J. B., Leybaert, L., Vereecke, J., Himpens, B., et al. (2012). RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system. PLOS ONE, 7(7).
Vancouver
1.
Ponsaerts R, D’Hondt C, Hertens F, Parys JB, Leybaert L, Vereecke J, et al. RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system. PLOS ONE. 2012;7(7).
MLA
Ponsaerts, Raf, Catheleyne D’Hondt, Fréderic Hertens, et al. “RhoA GTPase Switch Controls Cx43-hemichannel Activity Through the Contractile System.” PLOS ONE 7.7 (2012): n. pag. Print.