Manipulating Connexin Communication Channels: Use of Peptidomimetics and the Translational Outputs

Gap junctions are key components underpinning multicellularity. They provide cell to cell channel pathways that enable direct intercellular communication and cellular coordination in tissues and organs. The channels are constructed of a family of connexin (Cx) membrane proteins. They oligomerize ins...

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Main Authors:	Evans, W. Howard, Bultynck, Geert, Leybaert, Luc
Format:	Online
Language:	English
Published:	Springer-Verlag 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3456916/

id	pubmed-3456916
recordtype	oai_dc
spelling	pubmed-34569162012-09-28 Manipulating Connexin Communication Channels: Use of Peptidomimetics and the Translational Outputs Evans, W. Howard Bultynck, Geert Leybaert, Luc Topical Review Gap junctions are key components underpinning multicellularity. They provide cell to cell channel pathways that enable direct intercellular communication and cellular coordination in tissues and organs. The channels are constructed of a family of connexin (Cx) membrane proteins. They oligomerize inside the cell, generating hemichannels (connexons) composed of six subunits arranged around a central channel. After transfer to the plasma membrane, arrays of Cx hemichannels (CxHcs) interact and couple with partners in neighboring attached cells to generate gap junctions. Cx channels have been studied using a range of technical approaches. Short peptides corresponding to sequences in the extra- and intracellular regions of Cxs were used first to generate epitope-specific antibodies that helped studies on the organization and functions of gap junctions. Subsequently, the peptides themselves, especially Gap26 and -27, mimetic peptides derived from each of the two extracellular loops of connexin43 (Cx43), a widely distributed Cx, have been extensively applied to block Cx channels and probe the biology of cell communication. The development of a further series of short peptides mimicking sequences in the intracellular loop, especially the extremity of the intracellular carboxyl tail of Cx43, followed. The primary inhibitory action of the peptidomimetics occurs at CxHcs located at unapposed regions of the cell’s plasma membrane, followed by inhibition of cell coupling occurring across gap junctions. CxHcs respond to a range of environmental conditions by increasing their open probability. Peptidomimetics provide a way to block the actions of CxHcs with some selectivity. Furthermore, they are increasingly applied to address the pathological consequences of a range of environmental stresses that are thought to influence Cx channel operation. Cx peptidomimetics show promise as candidates in developing new therapeutic approaches for containing and reversing damage inflicted on CxHcs, especially in hypoxia and ischemia in the heart and in brain functions. Springer-Verlag 2012-08-11 2012-08 /pmc/articles/PMC3456916/ /pubmed/22886208 http://dx.doi.org/10.1007/s00232-012-9488-5 Text en © The Author(s) 2012
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Evans, W. Howard Bultynck, Geert Leybaert, Luc
spellingShingle	Evans, W. Howard Bultynck, Geert Leybaert, Luc Manipulating Connexin Communication Channels: Use of Peptidomimetics and the Translational Outputs
author_facet	Evans, W. Howard Bultynck, Geert Leybaert, Luc
author_sort	Evans, W. Howard
title	Manipulating Connexin Communication Channels: Use of Peptidomimetics and the Translational Outputs
title_short	Manipulating Connexin Communication Channels: Use of Peptidomimetics and the Translational Outputs
title_full	Manipulating Connexin Communication Channels: Use of Peptidomimetics and the Translational Outputs
title_fullStr	Manipulating Connexin Communication Channels: Use of Peptidomimetics and the Translational Outputs
title_full_unstemmed	Manipulating Connexin Communication Channels: Use of Peptidomimetics and the Translational Outputs
title_sort	manipulating connexin communication channels: use of peptidomimetics and the translational outputs
description	Gap junctions are key components underpinning multicellularity. They provide cell to cell channel pathways that enable direct intercellular communication and cellular coordination in tissues and organs. The channels are constructed of a family of connexin (Cx) membrane proteins. They oligomerize inside the cell, generating hemichannels (connexons) composed of six subunits arranged around a central channel. After transfer to the plasma membrane, arrays of Cx hemichannels (CxHcs) interact and couple with partners in neighboring attached cells to generate gap junctions. Cx channels have been studied using a range of technical approaches. Short peptides corresponding to sequences in the extra- and intracellular regions of Cxs were used first to generate epitope-specific antibodies that helped studies on the organization and functions of gap junctions. Subsequently, the peptides themselves, especially Gap26 and -27, mimetic peptides derived from each of the two extracellular loops of connexin43 (Cx43), a widely distributed Cx, have been extensively applied to block Cx channels and probe the biology of cell communication. The development of a further series of short peptides mimicking sequences in the intracellular loop, especially the extremity of the intracellular carboxyl tail of Cx43, followed. The primary inhibitory action of the peptidomimetics occurs at CxHcs located at unapposed regions of the cell’s plasma membrane, followed by inhibition of cell coupling occurring across gap junctions. CxHcs respond to a range of environmental conditions by increasing their open probability. Peptidomimetics provide a way to block the actions of CxHcs with some selectivity. Furthermore, they are increasingly applied to address the pathological consequences of a range of environmental stresses that are thought to influence Cx channel operation. Cx peptidomimetics show promise as candidates in developing new therapeutic approaches for containing and reversing damage inflicted on CxHcs, especially in hypoxia and ischemia in the heart and in brain functions.
publisher	Springer-Verlag
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3456916/
_version_	1611911558225461248

Manipulating Connexin Communication Channels: Use of Peptidomimetics and the Translational Outputs

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