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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 (CaV1) 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 CaV1E. CaV1E 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 CaV1E compared with young muscle, displaying an altered GDF5-dependent response to denervation. Conversely, CaV1E overexpression improved mass wasting in aging muscle in mice by increasing GDF5 expression. We also identified the human CaV1E analogous and show a correlation between CaV1E expression in human muscles and age-related muscle mass decline. These results suggest that strategies targeting CaV1E or GDF5 might be effective in reducing muscle mass loss in aging.
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https://hal.archives-ouvertes.fr/hal-02382706
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Submitted on : Tuesday, October 20, 2020 - 3:17:51 PM
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Massiré Traore, Christel Gentil, Chiara Benedetto, Jean-Yves Hogrel, Pierre de la Grange, et al.. An embryonic CaVβ1 isoform promotes muscle mass maintenance via GDF5 signaling in adult mouse. Science Translational Medicine, American Association for the Advancement of Science, 2019, ⟨10.1126/scitranslmed.aaw1131⟩. ⟨hal-02382706⟩

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