Cardiomyopathy related desmocollin-2 prodomain variants affect the intracellular cadherin transport and processing.

ABSTRACT:

Background

Arrhythmogenic cardiomyopathy can be caused by genetic variants in desmosomal cadherins. Since cardiac desmosomal cadherins are crucial for cell-cell-adhesion, their correct localization at the plasma membrane is essential.

Methods

Nine desmocollin-2 variants at five positions from various public genetic databases (p.D30N, p.V52A/I, p.G77V/D/S, p.V79G, p.I96V/T) and three additional conserved positions (p.C32, p.C57, p.F71) within the prodomain were investigated in vitro using confocal microscopy. Model variants (p.C32A/S, p.V52G/L, p.C57A/S, p.F71Y/A/S, p.V79A/I/L, p.I96l/A) were generated to investigate the impact of specific amino acids.

Results

We revealed that all analyzed positions in the prodomain are critical for the intracellular transport.

SUBMITTER: Pohl GM 

PROVIDER: S-EPMC10235514 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature