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Int. J. Mol. Sci. 2018, 19(5), 1428; https://doi.org/10.3390/ijms19051428

Protein–Protein Interactions with Connexin 43: Regulation and Function

1
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA
2
Leon H Charney Division of Cardiology, NYU School of Medicine, New York, NY 10016, USA
3
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Received: 20 April 2018 / Revised: 7 May 2018 / Accepted: 8 May 2018 / Published: 10 May 2018
(This article belongs to the Special Issue Interplay of Connexins and Pannexins in Tissue Function and Disease)
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Abstract

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. View Full-Text
Keywords: gap junction; connexin; protein–protein interaction; intrinsically disordered protein; post-translational modification; intercalated disc gap junction; connexin; protein–protein interaction; intrinsically disordered protein; post-translational modification; intercalated disc
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Sorgen, P.L.; Trease, A.J.; Spagnol, G.; Delmar, M.; Nielsen, M.S. Protein–Protein Interactions with Connexin 43: Regulation and Function. Int. J. Mol. Sci. 2018, 19, 1428.

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