Role of calcineurin B homologous protein 3 in C2C12 myogenic differentiation

Calcineurin B homologous protein 3 (CHP3), also known as tescalcin, has been implicated in the regulation of cardiomyocyte hypertrophy, but its function in skeletal muscle remains unclear. Here, we investigated the role of CHP3 in C2C12 myogenic differentiation. CHP3 expression was upregulated during the differentiation of mouse C2C12 myoblasts into myotubes. Genetic deletion of CHP3 impaired myogenic differentiation, as evidenced by reduced myogenin and myosin heavy chain (MHC) expression and myocyte fusion. These defects were accompanied by decreased phosphorylation of key signaling proteins involved in myogenic differentiation, including glycogen synthase kinase 3β (GSK3β), mammalian target of rapamycin (mTOR), and ribosomal protein S6 kinase beta-1 (p70S6K). In contrast, CHP3 overexpression enhanced myogenic differentiation and increased phosphorylation of these signaling proteins. Furthermore, co-immunoprecipitation assays revealed that CHP3 associates with GSK3β and mTOR. These findings indicate that CHP3 is a positive regulator of C2C12 myogenic differentiation and suggest that GSK3β and mTOR signaling may contribute to its effects.