Advanced search
1 file | 1.16 MB

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

(2012) PLOS ONE. 7(7).
Author
Organization
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.
Keywords
INTERCELLULAR CALCIUM WAVE, CORNEAL ENDOTHELIAL-CELLS, THROMBIN-INDUCED INHIBITION, GAP-JUNCTION CHANNELS, ATP RELEASE, MYOSIN-II, MEMBRANE PERMEABILIZATION, CONNEXIN HEMICHANNELS, ASTROCYTOMA-CELLS, COMMUNICATION

Downloads

  • Ponsaert 2012 PO 7 7 e42074.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 1.16 MB

Citation

Please use this url to cite or link to this publication:

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.
@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},
}

Altmetric
View in Altmetric
Web of Science
Times cited: