ArticleSkeletal muscle2024
The MuSK-BMP pathway maintains myofiber size in slow muscle through regulation of Akt-mTOR signaling.
Article in Skeletal muscle, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Inductive analysis of the spatial distribution characteristics of neurons that innervate skeletal muscle and their correlation with muscle phenotype.Neural regeneration research · 2026Article
- Mechanisms of protein degradation in atrophying muscles: What have we learned during the past decade?The Journal of biological chemistry · 2026Review
- Muscle-Derived BMP4 Regulates Morphology and Function of Endplates on Extrafusal and Intrafusal Muscle Fibers in Adult Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Molecular Framework of the Onset and Progression of Skeletal Muscle Aging.International journal of molecular sciences · 2025Review
- Insights into the bone morphogenetic protein signaling in musculoskeletal disorders: Mechanisms and crosstalk.Journal of orthopaedic translation · 2025Review
- MuSK Regulates Neuromuscular Junction Nav1.4 Localization and Excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Postsynaptic BMP signaling regulates myonuclear properties in Drosophila larval muscles.The Journal of cell biology · 2025Article
- The effects of TGF-β receptor I inhibitors on myofibroblast differentiation and myotube formation.Frontiers in cell and developmental biology · 2025Article
- Postsynaptic BMP signaling regulates myonuclear properties inbioRxiv : the preprint server for biology · 2024Article
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8 authors at 2 institutions in 2 countries.
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Abstract
Myofiber size regulation is critical in health, disease, and aging. MuSK (muscle-specific kinase) is a BMP (bone morphogenetic protein) co-receptor that promotes and shapes BMP signaling. MuSK is expressed at all neuromuscular junctions and is also present extrasynaptically in the mouse soleus, whose predominantly oxidative fiber composition is akin to that of human muscle. To investigate the role of the MuSK-BMP pathway in vivo, we generated mice lacking the BMP-binding MuSK Ig3 domain. These ∆Ig3-MuSK mice are viable and fertile with innervation levels comparable to wild type. In 3-month-old mice, myofibers are smaller in the slow soleus, but not in the fast tibialis anterior (TA). Transcriptomic analysis revealed soleus-selective decreases in RNA metabolism and protein synthesis pathways as well as dysregulation of IGF1-Akt-mTOR pathway components. Biochemical analysis showed that Akt-mTOR signaling is reduced in soleus but not TA. We propose that the MuSK-BMP pathway acts extrasynaptically to maintain myofiber size in slow muscle by promoting protein synthetic pathways including IGF1-Akt-mTOR signaling. These results reveal a novel mechanism for regulating myofiber size in slow muscle and introduce the MuSK-BMP pathway as a target for promoting muscle growth and combatting atrophy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.