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Review
. 2014 Jun;21(3):169-79.
doi: 10.3109/15419061.2014.908853. Epub 2014 Apr 28.

N-cadherin/catenin complex as a master regulator of intercalated disc function

Alexia Vite  1 , Glenn L Radice
Affiliations
Review

N-cadherin/catenin complex as a master regulator of intercalated disc function

Alexia Vite et al. Cell Commun Adhes. 2014 Jun.

Erratum in

  • Cell Commun Adhes. 2014 Dec;21(6):291

Abstract

Intercellular adhesive junctions are essential for maintaining the physical integrity of tissues; this is particularly true for the heart that is under constant mechanical load. The correct functionality of the heart is dependent on the electrical and mechanical coordination of its constituent cardiomyocytes. The intercalated disc (ID) structure located at the termini of the rod-shaped adult cardiomyocyte contains various junctional proteins responsible for the integration of structural information and cell-cell communication. According to the classical description, the ID consists of three distinct junctional complexes: adherens junction (AJ), desmosome (Des), and gap junction (GJ) that work together to mediate mechanical and electrical coupling of cardiomyocytes. However, recent morphological and molecular studies indicate that AJ and Des components are capable of mixing together resulting in a "hybrid adhering junction" or "area composita." This review summarizes recent progress in understanding the in vivo function(s) of AJ components in cardiac homeostasis and disease.

Keywords: N-cadherin; adherens junction; arrhythmogenic cardiomyopathy; catenin; desmosome.

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Conflict of interest statement

Conflict of interest

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Figures

Figure 1:
Figure 1:. Transmission electron microscopy of a cross section through intercalated disc of a mouse heart.
TEM image showing the intercalated disc with a large mixed-type junction (area composita) surrounded by two dense desmosome structures (black arrows).
Figure 2:
Figure 2:. Molecular organization of Area composita vs. desmosome in the heart.
a) Immunoelectron microscopy images of the myocardium of a mouse heart showing the co-localization of PKP2 and αT-catenin at the area composita. Note the absence of αT-catenin in the desmosome. These images were originally published in “J Cell Sci., Goosens et al. 2007”. b) Model for cadherin-based cell-cell adhesion in the heart. This model represents the composition of a hybrid junction compared to a desmosome. αT-catenin recruits desmosomal proteins through its interaction with plakophilin-2 (PKP2), forming a hybrid junction (named area composita), reinforcing the intercalated discs resistance. (αE: αE-catenin; αT: αT-catenin; β-cat: β-catenin; PG: Plakoglobin; PKP2: Plakophillin-2; IF: Intermediate Filaments).
Figure 3:
Figure 3:. Functional Hierarchy at the Intercalated Disc.
Scheme depicts the relationship between the different junctions and cardiac dysfunction.
Figure 4:
Figure 4:. Junctional proteins interactome.
The intercalated disc protein-protein interaction network is based on STRING v9.1 analysis (http://string-db.org/) using the default settings (Franceschini et al., 2013). Black lines represent direct interactions, while dotted lines represent assumed interactions based on studies of the structures homology. (Ncad: N-cadherin; B-cat: β-catenin; p120ctn: p120-catenin; PG: Plakoglobin; PKP2: Plakophillin-2; DSG2: Desmoglein-2; DSC2: Desmocollin-2; DSP: Desmoplakin; Cx43: Connexin-43; AnkG: Ankyrin G; Kv: Potassium channels; kChiP2: Kv channel-interacting protein 2; ACTN: Actinin).
See this image and copyright information in PMC

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