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Calcium-binding protein 7 expressed in muscle negatively regulates age-related degeneration of neuromuscular junctions in mice.
- Source :
-
IScience [iScience] 2024 Jan 26; Vol. 27 (2), pp. 108997. Date of Electronic Publication: 2024 Jan 26 (Print Publication: 2024). - Publication Year :
- 2024
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Abstract
- The neuromuscular junction (NMJ) forms centrally in myotubes and, as the only synapse between motor neuron and myotube, are indispensable for motor activity. The midmuscle formation of NMJs, including midmuscle-restricted expression of NMJ-related genes, is governed by the muscle-specific kinase (MuSK). However, mechanisms underlying MuSK-mediated signaling are unclear. Here, we find that the Calcium-binding protein 7 ( Cabp7 ) gene shows midmuscle-restricted expression, and muscle-specific depletion of Cabp7 in mice accelerated age-related NMJ degeneration, muscle weakness/atrophy, and motor dysfunction. Surprisingly, forced expression in muscle of CIP, an inhibitory peptide of the negative regulator of NMJ formation cyclin-dependent kinase 5 (Cdk5), restored NMJ integrity and muscle strength, and healed muscle atrophy in muscle-specific Cabp7-deficient mice, which showed increased muscle expression of the Cdk5 activator p25. These findings together demonstrate that MuSK-mediated signaling induces muscle expression of Cabp7, which suppresses age-related NMJ degeneration likely by attenuating p25 expression, providing insights into prophylactic/therapeutic intervention against age-related motor dysfunction.<br />Competing Interests: The authors declare no competing interests.<br /> (© 2024 The Author(s).)
Details
- Language :
- English
- ISSN :
- 2589-0042
- Volume :
- 27
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- IScience
- Publication Type :
- Academic Journal
- Accession number :
- 38327785
- Full Text :
- https://doi.org/10.1016/j.isci.2024.108997