The N-cadherin interactome in primary cardiomyocytes as defined using quantitative proximity proteomics

Area of Science:

• Cardiovascular Biology
• Cell Adhesion
• Proteomics

Background:

• Cardiomyocyte junctional complexes transmit mechanical forces and maintain adhesion.
• The adherens junction (AJ) links cardiomyocyte actomyosin networks, crucial for heart function.
• The molecular composition and organization of cardiomyocyte AJs under mechanical load are poorly understood.

Purpose of the Study:

• To define the architecture, dynamics, and proteome of the cardiomyocyte AJ.
• To identify the N-cadherin (CDH2) interactome in cardiomyocytes.
• To understand how AJs are organized to function under mechanical load.

Main Methods:

• Quantitative mass spectrometry
• Proximity labeling techniques
• Analysis of neonatal mouse cardiomyocytes

Main Results:

• Neonatal cardiomyocytes assemble stable AJs with mature hallmarks.
• Identified over 350 proteins in the N-cadherin (CDH2) interactome.
• Discovered nearly 200 CDH2-specific interactors, distinct from the E-cadherin (CDH1) interactome, including adaptor and adhesion proteins.

Conclusions:

• Provides a proteomic atlas of the cardiomyocyte AJ.
• Reveals novel insights into AJ composition and organization.
• Defines molecular complexes regulating cardiomyocyte intercellular adhesion.