| First Author | Eigler T | Year | 2021 |
| Journal | Dev Cell | Volume | 56 |
| Issue | 24 | Pages | 3349-3363.e6 |
| PubMed ID | 34932950 | Mgi Jnum | J:317032 |
| Mgi Id | MGI:6842881 | Doi | 10.1016/j.devcel.2021.11.022 |
| Citation | Eigler T, et al. (2021) ERK1/2 inhibition promotes robust myotube growth via CaMKII activation resulting in myoblast-to-myotube fusion. Dev Cell 56(24):3349-3363.e6 |
| abstractText | Myoblast fusion is essential for muscle development and regeneration. Yet, it remains poorly understood how mononucleated myoblasts fuse with preexisting fibers. We demonstrate that ERK1/2 inhibition (ERKi) induces robust differentiation and fusion of primary mouse myoblasts through a linear pathway involving RXR, ryanodine receptors, and calcium-dependent activation of CaMKII in nascent myotubes. CaMKII activation results in myotube growth via fusion with mononucleated myoblasts at a fusogenic synapse. Mechanistically, CaMKII interacts with and regulates MYMK and Rac1, and CaMKIIdelta/gamma knockout mice exhibit smaller regenerated myofibers following injury. In addition, the expression of a dominant negative CaMKII inhibits the formation of large multinucleated myotubes. Finally, we demonstrate the evolutionary conservation of the pathway in chicken myoblasts. We conclude that ERK1/2 represses a signaling cascade leading to CaMKII-mediated fusion of myoblasts to myotubes, providing an attractive target for the cultivated meat industry and regenerative medicine. |
