The Desmoglein 2 interactome in primary neonatal cardiomyocytes

Area of Science:

• Cardiovascular Biology
• Cell Adhesion
• Proteomics

Background:

• Intercalated discs (ICDs) are crucial for cardiomyocyte mechanical coupling and chemical communication.
• The protein network forming ICDs, essential for heart function, is not fully characterized.
• Understanding these protein complexes is vital for cardiac health.

Purpose of the Study:

• To identify proteins associated with Desmoglein 2 (DSG2) in cultured neonatal cardiomyocytes using proximity labeling and mass spectrometry.
• To define the protein interactome of DSG2 within the cardiomyocyte intercalated disc.
• To compare the DSG2 interactome with other known cardiac adhesion protein interactomes.

Main Methods:

• Proximity labeling techniques were employed to capture in vivo protein associations.
• Quantitative mass spectrometry was used to identify and quantify proteins in the DSG2 interactome.
• Bioinformatic analysis was performed to compare interactomes and identify unique and shared proteins.

Main Results:

• Over 300 proteins were identified in the DSG2 interactome of cardiomyocytes.
• Approximately 50% of the DSG2 interactome proteins were also found in the N-cadherin (CDH2) interactome.
• Unique DSG2 interactome proteins included connexin 43 and plakin family members; plakoglobin (JUP) and plakophilin 2 (PKP2) were abundant shared proteins.
• Few proteins were shared between cardiomyocyte DSG2 interactome and epithelial desmosomal protein interactomes.

Conclusions:

• The study provides a comprehensive proteomic map of the DSG2 interactome in cardiomyocytes.
• This reveals novel insights into the molecular composition of intercalated discs, particularly regarding adhesion and signaling complexes.
• The findings contribute significantly to the understanding of cardiomyocyte adhesion and cardiac function.