# The desmoglein 2 interactome in primary neonatal cardiomyocytes

## TL;DR

This study identifies over 300 proteins interacting with desmoglein 2 in heart cells, revealing unique and shared components important for cell adhesion.

## Contribution

The study provides the first detailed interactome of desmoglein 2 in cardiomyocytes, highlighting unique and shared proteins involved in cell adhesion.

## Key findings

- Over 300 proteins were identified in the DSG2 interactome in neonatal cardiomyocytes.
- Connexin 43 and plakin family proteins are unique to DSG2 in cardiomyocytes.
- Plakoglobin and plakophilin 2 are shared between DSG2 and CDH2 interactomes in cardiomyocytes.

## Abstract

Mechanical coupling and chemical communication between cardiomyocytes are facilitated through a specialized adhesive structure called the intercalated disc (ICD). The ICD is essential for heart organization and contraction. Yet, the network of adhesion, adaptor and signaling proteins that form the ICD remains poorly defined. Here, we combined proximity labeling and quantitative mass spectrometry to identify proteins associated with the desmosomal cadherin desmoglein 2 (DSG2), in cultured neonatal cardiomyocytes. We identified over 300 proteins in the DSG2 interactome, half of which are shared with the N-cadherin (CDH2) interactome in cardiomyocytes. Proteins unique to DSG2 include connexin 43 and the plakin family of cytolinker proteins. Comparison of the cardiomyocyte DSG2 interactome with the interactomes of desmosomal proteins from epithelia revealed few shared proteins. In cardiomyocytes, plakoglobin and plakophilin 2 (PKP2) were the most abundant shared proteins between the DSG2 and CDH2 interactomes. We show that PKP2 is a dynamic protein whose membrane recruitment in cardiomyocytes is dependent on tension. Our analysis of the DSG2 interactome provides a crucial new dimension to the proteomic atlas of the essential molecular complexes required for cardiomyocyte adhesion.

Highlighted Article:
The desmoglein 2 interactome in cultured neonatal cardiomyocytes reveals over 300 proteins, including unique desmosomal components and shared adhesion molecules.