| First Author | Traoré M | Year | 2019 |
| Journal | Sci Transl Med | Volume | 11 |
| Issue | 517 | PubMed ID | 31694926 |
| Mgi Jnum | J:294564 | Mgi Id | MGI:6455375 |
| Doi | 10.1126/scitranslmed.aaw1131 | Citation | Traore M, et al. (2019) An embryonic CaVbeta1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse. Sci Transl Med 11(517) |
| abstractText | Deciphering the mechanisms that govern skeletal muscle plasticity is essential to understand its pathophysiological processes, including age-related sarcopenia. The voltage-gated calcium channel CaV1.1 has a central role in excitation-contraction coupling (ECC), raising the possibility that it may also initiate the adaptive response to changes during muscle activity. Here, we revealed the existence of a gene transcription switch of the CaV1.1 beta subunit (CaVbeta1) that is dependent on the innervation state of the muscle in mice. In a mouse model of sciatic denervation, we showed increased expression of an embryonic isoform of the subunit that we called CaVbeta1E. CaVbeta1E boosts downstream growth differentiation factor 5 (GDF5) signaling to counteract muscle loss after denervation in mice. We further reported that aged mouse muscle expressed lower quantity of CaVbeta1E compared with young muscle, displaying an altered GDF5-dependent response to denervation. Conversely, CaVbeta1E overexpression improved mass wasting in aging muscle in mice by increasing GDF5 expression. We also identified the human CaVbeta1E analogous and show a correlation between CaVbeta1E expression in human muscles and age-related muscle mass decline. These results suggest that strategies targeting CaVbeta1E or GDF5 might be effective in reducing muscle mass loss in aging. |
