| First Author | Kim MJ | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 12 | Pages | e15355 |
| PubMed ID | 21179410 | Mgi Jnum | J:168998 |
| Mgi Id | MGI:4939528 | Doi | 10.1371/journal.pone.0015355 |
| Citation | Kim MJ, et al. (2010) Alpha-syntrophin modulates myogenin expression in differentiating myoblasts. PLoS One 5(12):e15355 |
| abstractText | BACKGROUND: alpha-Syntrophin is a scaffolding protein linking signaling proteins to the sarcolemmal dystrophin complex in mature muscle. However, alpha-syntrophin is also expressed in differentiating myoblasts during the early stages of muscle differentiation. In this study, we examined the relationship between the expression of alpha-syntrophin and myogenin, a key muscle regulatory factor. METHODS AND FINDINGS: The absence of alpha-syntrophin leads to reduced and delayed myogenin expression. This conclusion is based on experiments using muscle cells isolated from alpha-syntrophin null mice, muscle regeneration studies in alpha-syntrophin null mice, experiments in Sol8 cells (a cell line that expresses only low levels of alpha-syntrophin) and siRNA studies in differentiating C2 cells. In primary cultured myocytes isolated from alpha-syntrophin null mice, the level of myogenin was less than 50% that from wild type myocytes (p<0.005) 40 h after differentiation induction. In regenerating muscle, the expression of myogenin in the alpha-syntrophin null muscle was reduced to approximately 25% that of wild type muscle (p<0.005). Conversely, myogenin expression is enhanced in primary cultures of myoblasts isolated from a transgenic mouse over-expressing alpha-syntrophin and in Sol8 cells transfected with a vector to over-express alpha-syntrophin. Moreover, we find that myogenin mRNA is reduced in the absence of alpha-syntrophin and increased by alpha-syntrophin over-expression. Immunofluorescence microscopy shows that alpha-syntrophin is localized to the nuclei of differentiating myoblasts. Finally, immunoprecipitation experiments demonstrate that alpha-syntrophin associates with Mixed-Lineage Leukemia 5, a regulator of myogenin expression. CONCLUSIONS: We conclude that alpha-syntrophin plays an important role in regulating myogenesis by modulating myogenin expression. |
