| First Author | Lenhart KC | Year | 2014 |
| Journal | Dev Biol | Volume | 393 |
| Issue | 2 | Pages | 298-311 |
| PubMed ID | 25019370 | Mgi Jnum | J:215392 |
| Mgi Id | MGI:5605215 | Doi | 10.1016/j.ydbio.2014.06.025 |
| Citation | Lenhart KC, et al. (2014) GRAF1 promotes ferlin-dependent myoblast fusion. Dev Biol 393(2):298-311 |
| abstractText | Myoblast fusion (a critical process by which muscles grow) occurs in a multi-step fashion that requires actin and membrane remodeling; but important questions remain regarding the spatial/temporal regulation of and interrelationship between these processes. We recently reported that the Rho-GAP, GRAF1, was particularly abundant in muscles undergoing fusion to form multinucleated fibers and that enforced expression of GRAF1 in cultured myoblasts induced robust fusion by a process that required GAP-dependent actin remodeling and BAR domain-dependent membrane sculpting. Herein we developed a novel line of GRAF1-deficient mice to explore a role for this protein in the formation/maturation of myotubes in vivo. Post-natal muscles from GRAF1-depleted mice exhibited a significant and persistent reduction in cross-sectional area, impaired regenerative capacity and a significant decrease in force production indicative of lack of efficient myoblast fusion. A significant fusion defect was recapitulated in isolated myoblasts depleted of GRAF1 or its closely related family member GRAF2. Mechanistically, we show that GRAF1 and 2 facilitate myoblast fusion, at least in part, by promoting vesicle-mediated translocation of fusogenic ferlin proteins to the plasma membrane. |
