Intracellular Cleavage of the Cx43 C-Terminal Domain by Matrix-Metalloproteases: A Novel Contributor to InflammationReport as inadecuate




Intracellular Cleavage of the Cx43 C-Terminal Domain by Matrix-Metalloproteases: A Novel Contributor to Inflammation - Download this document for free, or read online. Document in PDF available to download.

Mediators of Inflammation - Volume 2015 2015, Article ID 257471, 18 pages -

Review Article

Physiology Group, Department of Basic Medical Sciences, Ghent University, 9000 Ghent, Belgium

Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium

Received 12 July 2015; Accepted 13 August 2015

Academic Editor: Mauro Prato

Copyright © 2015 Marijke De Bock et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The coordination of tissue function is mediated by gap junctions GJs that enable direct cell-cell transfer of metabolic and electric signals. GJs are formed by connexin Cx proteins of which Cx43 is most widespread in the human body. Beyond its role in direct intercellular communication, Cx43 also forms nonjunctional hemichannels HCs in the plasma membrane that mediate the release of paracrine signaling molecules in the extracellular environment. Both HC and GJ channel function are regulated by protein-protein interactions and posttranslational modifications that predominantly take place in the C-terminal domain of Cx43. Matrix metalloproteases MMPs are a major group of zinc-dependent proteases, known to regulate not only extracellular matrix remodeling, but also processing of intracellular proteins. Together with Cx43 channels, both GJs and HCs, MMPs contribute to acute inflammation and a small number of studies reports on an MMP-Cx43 link. Here, we build further on these reports and present a novel hypothesis that describes proteolytic cleavage of the Cx43 C-terminal domain by MMPs and explores possibilities of how such cleavage events may affect Cx43 channel function. Finally, we set out how aberrant channel function resulting from cleavage can contribute to the acute inflammatory response during tissue injury.





Author: Marijke De Bock, Nan Wang, Elke Decrock, Geert Bultynck, and Luc Leybaert

Source: https://www.hindawi.com/



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