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

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...

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Autores principales:	Raf Ponsaerts, Catheleyne D'hondt, Fréderic Hertens, Jan B Parys, Luc Leybaert, Johan Vereecke, Bernard Himpens, Geert Bultynck
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e05cc799374647eaa29d5c02e7075e33
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spelling	oai:doaj.org-article:e05cc799374647eaa29d5c02e7075e332021-11-18T07:10:23ZRhoA GTPase switch controls Cx43-hemichannel activity through the contractile system.1932-620310.1371/journal.pone.0042074https://doaj.org/article/e05cc799374647eaa29d5c02e7075e332012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22860057/?tool=EBIhttps://doaj.org/toc/1932-6203ATP-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.Raf PonsaertsCatheleyne D'hondtFréderic HertensJan B ParysLuc LeybaertJohan VereeckeBernard HimpensGeert BultynckPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e42074 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Raf Ponsaerts Catheleyne D'hondt Fréderic Hertens Jan B Parys Luc Leybaert Johan Vereecke Bernard Himpens Geert Bultynck RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system.
description	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.
format	article
author	Raf Ponsaerts Catheleyne D'hondt Fréderic Hertens Jan B Parys Luc Leybaert Johan Vereecke Bernard Himpens Geert Bultynck
author_facet	Raf Ponsaerts Catheleyne D'hondt Fréderic Hertens Jan B Parys Luc Leybaert Johan Vereecke Bernard Himpens Geert Bultynck
author_sort	Raf Ponsaerts
title	RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system.
title_short	RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system.
title_full	RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system.
title_fullStr	RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system.
title_full_unstemmed	RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system.
title_sort	rhoa gtpase switch controls cx43-hemichannel activity through the contractile system.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e05cc799374647eaa29d5c02e7075e33
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RhoA GTPase switch controls Cx43-hemichannel activity through the contractile system.

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