Fig. 7
Nav1.5 interacts with β-catenin. A Nav1.5 was detected in the immunoprecipitation pull-down lysate from control iPSC-CMs using antibody against β-catenin, indicating that Nav1.5 interacts with β-catenin. IP: β-catenin, IP with β-catenin antibody. Full-length blots are presented in Additional file 1: Fig. S14. B β-catenin was detected in the immunoprecipitation pull-down lysate from control iPSC-CMs using antibody against Nav1.5, indicating that β-catenin interacts with Nav1.5. IP: Nav1.5, IP with Nav1.5 antibody. Full-length blots are presented in Additional file 1: Fig. S15. C Representative confocal images of β-catenin (green) and Nav1.5(red) staining in control and BrS iPSC-CMs, showing the co-localization of Nav1.5 and β-catenin in iPSC-CMs. Scale bar, 20 μm. D Schematic representation of the proposed mechanism of SCN5A-T1788fs action in cardiomyocytes. Left: In control iPSC-CMs, β-catenin is mainly localized in the cell membrane with Nav1.5. Cytoplasmic β-catenin is at a low level and is degraded by the destruction complex. Right: In BrS iPSC-CMs carrying the SCN5A-T1788fs mutation, the loss of Nav1.5 disturbs the distribution of β-catenin and subsequently increases nuclear localization of β-catenin, which leads to the suppression of SCN5A transcription. Thus, a vicious circle is formed to cause arrhythmias in mutant myocytes