| Centre de recherche en myologie |  |
Journal articles
An embryonic CaVβ1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse
Abstract : 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 subunit (CaV1) 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 CaV1E. CaV1E 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 CaV1E compared with young muscle, displaying an altered GDF5-dependent response to denervation. Conversely, CaV1E overexpression improved mass wasting in aging muscle in mice by increasing GDF5 expression. We also identified the human CaV1E analogous and show a correlation between CaV1E expression in human muscles and age-related muscle mass decline. These results suggest that strategies targeting CaV1E or GDF5 might be effective in reducing muscle mass loss in aging.
Cited literature [3 references]
https://hal.archives-ouvertes.fr/hal-02382706
Contributor : France Piétri-Rouxel <>
Submitted on : Tuesday, October 20, 2020 - 3:17:51 PM
Last modification on : Monday, December 14, 2020 - 9:53:05 AM
Long-term archiving on: : Thursday, January 21, 2021 - 6:02:01 PM
Contributor : France Piétri-Rouxel <>
Submitted on : Tuesday, October 20, 2020 - 3:17:51 PM
Last modification on : Monday, December 14, 2020 - 9:53:05 AM
Long-term archiving on: : Thursday, January 21, 2021 - 6:02:01 PM