ArticleScience signaling2016
MuSK is a BMP co-receptor that shapes BMP responses and calcium signaling in muscle cells.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Muscle-Specific Kinase Signaling and Its Therapeutic Potential.Muscle & nerve · 2026Review
- Understanding of the different roles of Noggin in the Noggin-BMP-2 and Noggin-BMP-9 dimer complexes at the molecular level.Scientific reports · 2026Article
- The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Injectable therapeutic system incorporating neurogenesis-programmed stem cells concomitantly promoting muscle regeneration treats stress urinary incontinence.Nature communications · 2025Article
- 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
- Article
- Postsynaptic BMP signaling regulates myonuclear properties inbioRxiv : the preprint server for biology · 2024Article
- The MuSK-BMP pathway maintains myofiber size in slow muscle through regulation of Akt-mTOR signaling.Skeletal muscle · 2024Article
- A clinical perspective on muscle specific kinase antibody positive myasthenia gravis.Frontiers in immunology · 2024Review
- IgG1-3 MuSK Antibodies Inhibit AChR Cluster Formation, Restored by SHP2 Inhibitor, Despite Normal MuSK, DOK7, or AChR Subunit Phosphorylation.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- The context-dependent, combinatorial logic of BMP signaling.Cell systems · 2022Article
- iMyoblasts for ex vivo and in vivo investigations of human myogenesis and disease modeling.eLife · 2022Article
- TGF-β superfamily co-receptors in cancer.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Review
- Secreted Signaling Molecules at the Neuromuscular Junction in Physiology and Pathology.International journal of molecular sciences · 2021Review
- Review
- Multiple MuSK signaling pathways and the aging neuromuscular junction.Neuroscience letters · 2020Review
- Myasthenia Gravis: From the Viewpoint of Pathogenicity Focusing on Acetylcholine Receptor Clustering, Trans-Synaptic Homeostasis and Synaptic Stability.Frontiers in molecular neuroscience · 2020Article
- Tyrosine kinase Eph receptor A6 sensitizes glioma-initiating cells towards bone morphogenetic protein-induced apoptosis.Cancer science · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Bone morphogenetic proteins (BMPs) function in most tissues but have cell type-specific effects. Given the relatively small number of BMP receptors, this exquisite signaling specificity requires additional molecules to regulate this pathway's output. The receptor tyrosine kinase MuSK (muscle-specific kinase) is critical for neuromuscular junction formation and maintenance. Here, we show that MuSK also promotes BMP signaling in muscle cells. MuSK bound to BMP4 and related BMPs with low nanomolar affinity in vitro and to the type I BMP receptors ALK3 and ALK6 in a ligand-independent manner both in vitro and in cultured myotubes. High-affinity binding to BMPs required the third, alternatively spliced MuSK immunoglobulin-like domain. In myoblasts, endogenous MuSK promoted BMP4-dependent phosphorylation of SMADs and transcription of Id1, which encodes a transcription factor involved in muscle differentiation. Gene expression profiling showed that MuSK was required for the BMP4-induced expression of a subset of genes in myoblasts, including regulator of G protein signaling 4 (Rgs4). In myotubes, MuSK enhanced the BMP4-induced expression of a distinct set of genes, including transcripts characteristic of slow muscle. MuSK-mediated stimulation of BMP signaling required type I BMP receptor activity but was independent of MuSK tyrosine kinase activity. MuSK-dependent expression of Rgs4 resulted in the inhibition of Ca(2+) signaling induced by the muscarinic acetylcholine receptor in myoblasts. These findings establish that MuSK has dual roles in muscle cells, acting both as a tyrosine kinase-dependent synaptic organizing molecule and as a BMP co-receptor that shapes BMP transcriptional output and cholinergic signaling.
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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.