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Intercalated discs: cellular adhesion and signaling in heart health and diseases

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Abstract

Intercalated discs (ICDs) are highly orchestrated structures that connect neighboring cardiomyocytes in the heart. Three major complexes are distinguished in ICD: desmosome, adherens junction (AJ), and gap junction (GJ). Desmosomes are major cell adhesion junctions that anchor cell membrane to the intermediate filament network; AJs connect the actin cytoskeleton of adjacent cells; and gap junctions metabolically and electrically connect the cytoplasm of adjacent cardiomyocytes. All these complexes work as a single unit, the so-called area composita, interdependently rather than individually. Mutation or altered expression of ICD proteins results in various cardiac diseases, such as ARVC (arrhythmogenic right ventricular cardiomyopathy), dilated cardiomyopathy, and hypotrophy cardiomyopathy, eventually leading to heart failure. In this article, we first review the recent findings on the structural organization of ICD and their functions and then focus on the recent advances in molecular pathogenesis of the ICD-related heart diseases, which include two major areas: i) the ICD gene mutations in cardiac diseases, and ii) the involvement of ICD proteins in signal transduction pathways leading to myocardium remodeling and eventual heart failure. These major ICD-related signaling pathways include Wnt/β-catenin pathway, p38 MAPK cascade, Rho-dependent serum response factor (SRF) signaling, calcineurin/NFAT signaling, Hippo kinase cascade, etc., which are differentially regulated in pathological conditions.

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Funding

This work was supported by a grant from the Canadian Institutes of Health Research (Grant # MOP 125999) and Heart and Stroke Foundation of Canada (G-16-00014152).

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada

    Guangze Zhao, Huifang M. Zhang & Decheng Yang

  2. Center for Heart Lung Innovation - St. Paul’s Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada

    Guangze Zhao, Huifang M. Zhang & Decheng Yang

  3. College of Biology, Hunan Universsity, Changsha, China

    Ye Qiu

Authors
  1. Guangze Zhao
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  2. Ye Qiu
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  3. Huifang M. Zhang
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  4. Decheng Yang
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Corresponding author

Correspondence to Decheng Yang.

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Zhao, G., Qiu, Y., Zhang, H.M. et al. Intercalated discs: cellular adhesion and signaling in heart health and diseases. Heart Fail Rev 24, 115–132 (2019). https://doi.org/10.1007/s10741-018-9743-7

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  • DOI: https://doi.org/10.1007/s10741-018-9743-7

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