Protein–Protein Interactions with Connexin 43: Regulation and Function

International Journal of Molecular Sciences

Gaelle Spagnol¹  PaulL. Sorgen¹  AndrewJ. Trease¹  MortenS. Nielsen²  Mario Delmar³ 

[1] Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA;Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark;Leon H Charney Division of Cardiology, NYU School of Medicine, New York, NY 10016, USA;

关键词: gap junction;    connexin;    protein–protein interaction;    intrinsically disordered protein;    post-translational modification;    intercalated disc;   

DOI  :  10.3390/ijms19051428

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown