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

  title={Intercalated discs: cellular adhesion and signaling in heart health and diseases},
  author={Guangze Zhao and Ye Qiu and Huifang M. Zhang and Decheng Yang},
  journal={Heart Failure Reviews},
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… 

Structure and regulation of desmosomes in intercalated discs: Lessons from epithelia

The structural properties of ICD compared to epithelial desmosomes are described and it is suggested that mechanisms regulating adhesion may at least in part be comparable and phenomena such as hyperadhesion or the bidirectional regulation of desmosome to serve as signalling hubs in epithelial cells may also be relevant for ICD.

Adrenergic Signaling-Induced Ultrastructural Strengthening of Intercalated Discs via Plakoglobin Is Crucial for Positive Adhesiotropy in Murine Cardiomyocytes

The data demonstrate that in murine hearts adrenergic signaling enhanced N-cad and Dsg2 in the ICD paralleled by ultrastrutural strengthening of ICDs and that effects induced by positive adhesiotropy were strictly dependent on Pg.

Affimers targeting proteins in the cardiomyocyte Z-disc: Novel tools that improve imaging of heart tissue

The small size of the Affimer reagents, combined with a small linkage error revealed new structural details in Z-discs and intercalated discs in the failing samples, useful for analysis of changes to cardiomyocyte structure and organisation in diseased hearts.

Lipoprotein receptor‐related protein 6 is required to maintain intercalated disk integrity

LRP6 is required to maintain the integrity of ID structure and the balance of ID proteins, and the interaction between LRP6 and Cx43, N‐cadherin and γ‐catenin may be involved in this process.

Tmem65 is critical for the structure and function of the intercalated discs in mouse hearts

It is concluded that knockingdown of the ICD-bound transmembrane protein 65 results in impaired ICD structure, abnormal cardiac electrophysiology and cardiomyopathy in mice.

Immunoglobulin kappa light chain produced by cardiomyocytes and participates in maintaining intercalated disc integrity

Igκ expressed by cardiomyocytes is identified as a new ICD-related molecule that participates in cardiomeocyte contraction and conduction by stabilizing plectin.

Compromised Biomechanical Properties, Cell–Cell Adhesion and Nanotubes Communication in Cardiac Fibroblasts Carrying the Lamin A/C D192G Mutation

Investigation of the biophysical and biomechanical impact of the LMNA D192G mutation on neonatal rat ventricular fibroblasts finds that cytoskeleton disorganization, decreased elasticity of NRVFs, and altered cell–cell adhesion properties could explain how this mutation influences cardiac biomechanicals pathology and the severity of ACM in LMNA-cardiomyopathy.

Fine structure of the intercalated disc and cardiac junctions in the black widow spider Latrodectus mactans

This work investigated the fine structural features of intercalated discs and cardiac junctions of cardiac muscle cells in the black widow spider Latrodectus mactans, which has typical striated features and represents a functional syncytium that supports multiple connections to adjacent cells by intercalations.

Desmosomes: Essential contributors to an integrated intercellular junction network

Here, it is reviewed how desmosomes conferred new mechanical and signaling properties to vertebrate cells and tissues through their interactions with the existing junctional and cytoskeletal network.



Intercalated Discs and Arrhythmogenic Cardiomyopathy

This review highlights recent advances in understanding the link between ID alterations and the molecular genetics and pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC).

Refining the molecular organization of the cardiac intercalated disc

An extensively integrated model of the cardiac intercalated disc (ID), a highly orchestrated structure that connects adjacent cardiomyocytes, is presented, illustrating the interdependencies of ID proteins.

Intercalated discs: multiple proteins perform multiple functions in non-failing and failing human hearts

Clusters are grouped into clusters that demonstrate functionally interactive groups of proteins demonstrating that ICDs play a key role in cardiomyocyte function.

Cell-cell connection to cardiac disease.

Adrenergic Signaling Strengthens Cardiac Myocyte Cohesion

Positive adhesiotropy is shown as a new cardiac function of sympathetic signaling dependent on Pg phosphorylation at S665 by protein kinase A, and this mechanism may be of high medical relevance because loss of junctional Pg is a hallmark of arrhythmogenic cardiomyopathy.

Cardiac-Myocyte-Specific Excision of the Vinculin Gene Disrupts Cellular Junctions, Causing Sudden Death or Dilated Cardiomyopathy

This is the first report of tissue-specific inactivation of the Vcl gene and shows that it is required for preservation of normal cell-cell and cell-matrix adhesive structures.

Induced Deletion of the N-Cadherin Gene in the Heart Leads to Dissolution of the Intercalated Disc Structure

This animal model provides the first demonstration of the hierarchical relationship of the structural components of the intercalated disc in the working myocardium, thus establishing N-cadherin’s paramount importance in maintaining the structural integrity of the heart.

Ordered Assembly of the Adhesive and Electrochemical Connections within Newly Formed Intercalated Disks in Primary Cultures of Adult Rat Cardiomyocytes

The consistent order of the assembly process suggests that there are specific scaffolding requirements for integration of the mechanical and electrochemical elements of the disk.