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Protein–Protein Interactions with Connexin 43: Regulation and Function

Connexins are integral membrane building blocks that form gap junctions, enabling direct cytoplasmic exchange of ions and low-molecular-mass metabolites between adjacent cells. In the heart, gap junctions mediate the propagation of cardiac action potentials and the maintenance of a regular beating r...

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Autores principales: Sorgen, Paul L., Trease, Andrew J., Spagnol, Gaelle, Delmar, Mario, Nielsen, Morten S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983787/
https://www.ncbi.nlm.nih.gov/pubmed/29748463
http://dx.doi.org/10.3390/ijms19051428
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author Sorgen, Paul L.
Trease, Andrew J.
Spagnol, Gaelle
Delmar, Mario
Nielsen, Morten S.
author_facet Sorgen, Paul L.
Trease, Andrew J.
Spagnol, Gaelle
Delmar, Mario
Nielsen, Morten S.
author_sort Sorgen, Paul L.
collection PubMed
description Connexins are integral membrane building blocks that form gap junctions, enabling direct cytoplasmic exchange of ions and low-molecular-mass metabolites between adjacent cells. In the heart, gap junctions mediate the propagation of cardiac action potentials and the maintenance of a regular beating rhythm. A number of connexin interacting proteins have been described and are known gap junction regulators either through direct effects (e.g., kinases) or the formation of larger multifunctional complexes (e.g., cytoskeleton scaffold proteins). Most connexin partners can be categorized as either proteins promoting coupling by stimulating forward trafficking and channel opening or inhibiting coupling by inducing channel closure, internalization, and degradation. While some interactions have only been implied through co-localization using immunohistochemistry, others have been confirmed by biophysical methods that allow detection of a direct interaction. Our understanding of these interactions is, by far, most well developed for connexin 43 (Cx43) and the scope of this review is to summarize our current knowledge of their functional and regulatory roles. The significance of these interactions is further exemplified by demonstrating their importance at the intercalated disc, a major hub for Cx43 regulation and Cx43 mediated effects.
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spelling pubmed-59837872018-06-05 Protein–Protein Interactions with Connexin 43: Regulation and Function Sorgen, Paul L. Trease, Andrew J. Spagnol, Gaelle Delmar, Mario Nielsen, Morten S. Int J Mol Sci Review Connexins are integral membrane building blocks that form gap junctions, enabling direct cytoplasmic exchange of ions and low-molecular-mass metabolites between adjacent cells. In the heart, gap junctions mediate the propagation of cardiac action potentials and the maintenance of a regular beating rhythm. A number of connexin interacting proteins have been described and are known gap junction regulators either through direct effects (e.g., kinases) or the formation of larger multifunctional complexes (e.g., cytoskeleton scaffold proteins). Most connexin partners can be categorized as either proteins promoting coupling by stimulating forward trafficking and channel opening or inhibiting coupling by inducing channel closure, internalization, and degradation. While some interactions have only been implied through co-localization using immunohistochemistry, others have been confirmed by biophysical methods that allow detection of a direct interaction. Our understanding of these interactions is, by far, most well developed for connexin 43 (Cx43) and the scope of this review is to summarize our current knowledge of their functional and regulatory roles. The significance of these interactions is further exemplified by demonstrating their importance at the intercalated disc, a major hub for Cx43 regulation and Cx43 mediated effects. MDPI 2018-05-10 /pmc/articles/PMC5983787/ /pubmed/29748463 http://dx.doi.org/10.3390/ijms19051428 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Sorgen, Paul L.
Trease, Andrew J.
Spagnol, Gaelle
Delmar, Mario
Nielsen, Morten S.
Protein–Protein Interactions with Connexin 43: Regulation and Function
title Protein–Protein Interactions with Connexin 43: Regulation and Function
title_full Protein–Protein Interactions with Connexin 43: Regulation and Function
title_fullStr Protein–Protein Interactions with Connexin 43: Regulation and Function
title_full_unstemmed Protein–Protein Interactions with Connexin 43: Regulation and Function
title_short Protein–Protein Interactions with Connexin 43: Regulation and Function
title_sort protein–protein interactions with connexin 43: regulation and function
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983787/
https://www.ncbi.nlm.nih.gov/pubmed/29748463
http://dx.doi.org/10.3390/ijms19051428
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