Desmoglein-2 interaction is crucial for cardiomyocyte cohesion and function

Area of Science:

• Cardiovascular Biology
• Cell Adhesion
• Molecular Cardiology

Background:

• Cardiomyocytes rely on intercalated discs for mechanical and electrical coupling.
• Desmoglein-2, a desmosomal cadherin, is localized in intercalated discs alongside N-cadherin and gap junctions.
• The precise role of desmoglein-2 in cardiomyocyte cell-cell cohesion remains to be fully elucidated.

Purpose of the Study:

• To determine the contribution of desmoglein-2 to cell-cell cohesion in cardiomyocytes.
• To investigate the impact of desmoglein-2 modulation on cardiac cell adhesion and function.

Main Methods:

• Immunostaining of desmoglein-2 and N-cadherin in HL-1 cardiomyocytes.
• Measurement of cell-cell cohesion using dissociation assays and atomic force microscopy.
• Assessment of L-tryptophan and peptide effects on desmoglein-2 and N-cadherin interactions.
• Analysis of cardiac function in murine Langendorff hearts and heart slices.

Main Results:

• L-tryptophan impaired desmoglein-2 condensation and weakened cell-cell cohesion, affecting both desmoglein-2 and N-cadherin interactions.
• Specific peptides targeting desmoglein-2 blocked its inhibitory effects, confirming its role in adhesion.
• Desmoglein-2 knockdown and mutations associated with arrhythmogenic cardiomyopathy reduced cohesion, while overexpression enhanced it.
• Functional studies revealed impaired cardiomyocyte function and adrenergic response in hearts treated with L-tryptophan or desmoglein-2-specific peptides.

Conclusions:

• Desmoglein-2 plays a critical role in maintaining cardiomyocyte cohesion.
• Targeting desmoglein-2-mediated adhesion offers potential therapeutic avenues for cardiac disorders.
• Desmoglein-2 is crucial for overall cardiomyocyte function and response to stimuli.