title: Refining the molecular organization of the cardiac intercalated disc.
abstract: This review presents an extensively integrated model of the cardiac intercalated disc (ID), a highly orchestrated structure that connects adjacent cardiomyocytes. Classically, three main structures are distinguished: gap junctions (GJs) metabolically and electrically connect cytoplasm of adjacent cardiomyocytes; adherens junctions (AJs) connect the actin cytoskeleton of adjacent cells; and desmosomes function as cell anchors and connect intermediate filaments. Furthermore, ion channels reside in the ID. Mutations in ID proteins have been associated with cardiac arrhythmias such as Brugada syndrome and arrhythmogenic cardiomyopathy. However, rather than being independent, all ID components work together intensively by multifunctional proteins such as ZO-1, Ankyrin G, and β-catenin, integrating mechanical and electrical functions. GJs form a plaque surrounded by the perinexus in which free connexons reside; the connexome integrates NaV channels, the desmosome and GJs; and the area composita hosts AJs and desmosomes, also integrated as adhering junctions. Furthermore, the transitional junction connects sarcomeres to the plasma membrane. Lastly, this review integrates all these findings in comprehensible figures, illustrating the interdependencies of ID proteins.
authors.affiliation: Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.|Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Vermij
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Hugues
authors.initials: H
authors.lastname: Abriel
authors.affiliation: Department of Medical Physiology, Division of Heart & Lungs, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Toon A B
authors.initials: TA
authors.lastname: van Veen
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002450:Cell Communication; D003896:Desmosomes / Q000378:metabolism / Q000473:pathology; D017629:Gap Junctions / Q000378:metabolism / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007473:Ion Channels / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins
keywords: Arrhythmogenic cardiomyopathy; Brugada syndrome; Cardiac arrhythmia; Intercalated disc; Wnt signaling