Figure 7.
Schematic representation of the ERK1/2-CaMKII secondary fusion pathway
Schematic of the ERK-CaMKII signaling pathway during myoblast differentiation and fusion: (1) In proliferating myoblasts ERK1/2 suppresses MYOG and p21/p27 activation. (2) Upon ERK1/2 inhibition, p21/p27 are expressed and cells exit the cell cycle; simultaneously, MYOG is upregulated and cells differentiate. (3) During the differentiation process, ERK1/2 inhibition results in reduced phosphoinhibition of RXR leading to RYR1/3 upregulation and accumulation in early myotubes. RYR activity promotes in Ca2+-dependent CaMKII activation and CaMKII-dependent myotube driven asymmetric fusion, likely through CaMKII regulation of MYMK and Rac1.