Fig. 6

Schematic illustration of the mechanisms of Wnt/β-catenin signaling in untreated and treated (N-cadherin/CHIR99021) matured cardiomyocytes. a In untreated matured cardiomyocytes, the N-cadherin regulates the Wnt signaling by binding and sequestering cytoplasmic β-catenin at the cell membrane, hence reducing the amount of unbound cytoplasmic β-catenin that can be translocated into the nucleus. In addition, cytoplasmic β-catenin is also regulated by destruction complex, which will phosphorylate cytoplasmic β-catenin and targets it for ubiquitination and proteolysis. b Neutralizing N-cadherin signaling by N-cadherin antibody prevents the sequestration of β-catenin at the cell membrane which consequently leads to the release of membrane-bound β-catenin, resulting in a larger reservoir of cytoplasmic β-catenin that gets translocated into the nucleus to activate Wnt signaling for cardioproliferation. However, the function of N-cadherin in cell adherence is also disrupted by N-cadherin antibody treatment. c GSK inhibitor, CHIR99021, inhibits the function of β-catenin destruction complex and thus prevents the degradation of cytoplasmic β-catenin, resulting in a larger reservoir of cytoplasmic β-catenin that gets translocated into the nucleus to activate Wnt signaling for cardioproliferation. Note that CHIR99021 treatment does not affect cell adhesion, an important factor in cardioproliferation