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RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system
Raf Ponsaerts1, Catheleyne D'hondt, Fréderic Hertens
1Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Campus Gasthuisberg O/N-1, Faculty of Medicine, KU Leuven, Leuven, Belgium.
Plos One
|August 4, 2012
Summary
RhoA activation inhibits connexin 43 (Cx43) hemichannel activity, blocking ATP release crucial for cell communication. This finding reveals RhoA as a key regulator of Cx43 hemichannels during inflammatory responses.
Area of Science:
- Cellular Biology
- Molecular Signaling
- Biophysics
Background:
- Connexin 43 (Cx43) hemichannels mediate ATP release for paracrine signaling, requiring tight regulation for cell viability.
- Inflammatory mediators like thrombin and histamine inhibit Cx43 hemichannel activity in bovine corneal endothelial cells (BCECs).
Purpose of the Study:
- To investigate the role of RhoA activation in the thrombin-induced inhibition of hemichannel-mediated ATP release in BCECs.
Main Methods:
- Assessed RhoA activation kinetics upon thrombin stimulation in BCECs.
- Correlated RhoA activity with actomyosin contractility and Cx43 hemichannel function.
- Utilized C3-toxin pre-treatment and RhoA siRNA knockdown to block RhoA activity.
Main Results:
- RhoA activation was rapid and transient following thrombin treatment in BCECs.
- RhoA activity correlated with actomyosin contractility, which inhibits Cx43 hemichannels.
- Inhibition of RhoA activity prevented both RhoA activation and the suppression of Cx43 hemichannel function.
Conclusions:
- RhoA activation is a critical mediator of thrombin-induced inhibition of Cx43 hemichannel activity.
- RhoA acts as a molecular switch controlling Cx43 hemichannel function and ATP-dependent paracrine signaling under stress conditions.
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