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

  • Guangze Zhao
  • Ye Qiu
  • Huifang M. Zhang
  • Decheng Yang
Article

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.

Keywords

Intercalated disc Desmosome Adherens junction Gap junction Signaling Cardiomyopathy 

Notes

Funding information

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).

Compliance with ethical standards

Ethical standard

The manuscript does not contain clinical studies or patient data.

Conflict of interest

The authors declare that they have no conflict of interest. This has been also indicated in our cover letter.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada
  2. 2.Center for Heart Lung Innovation - St. Paul’s HospitalUniversity of British ColumbiaVancouverCanada
  3. 3.College of BiologyHunan UniverssityChangshaChina

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