ArticleGenes & development2012
Structural basis of agrin-LRP4-MuSK signaling.
Article in Genes & development, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 179 citations in OpenAlex.
- Pragmatic Phenotype-Electrophysiology-Genomics Integration in Pediatric Congenital Myasthenic Syndromes: Insights From 36 Patients in a Single-Center Study in China.CNS neuroscience & therapeutics · 2026Article
- Muscle-Specific Kinase Signaling and Its Therapeutic Potential.Muscle & nerve · 2026Review
- An S752D activation loop mutation dynamically primes Muscle-Specific Kinase for activation.The Biochemical journal · 2026Article
- Review
- Low Prevalence and Inconsistency of LRP4-IgG Detection in Suspected Myasthenia Gravis: A Multicenter CBA Comparison.Neurology(R) neuroimmunology & neuroinflammation · 2026Observational
- Article
- Adipocytic sclerostin loop3-LRP4 interaction required by sclerostin to impair whole-body lipid and glucose metabolism.Nature communications · 2026Article
- Diagnostic Challenges of LRP4 Antibody Testing in Myasthenia Gravis: A Case Series of Four LRP4 Positive Cases With Uncertain Diagnostic Significance.Case reports in neurological medicine · 2026Article
- MuSK myasthenia gravis: from antigen-antibody to clinical translation.Frontiers in immunology · 2026Review
- The neuromuscular junction: a critical component of functional recovery after peripheral nerve injury.Frontiers in surgery · 2026Review
- Regulation of motor neuron differentiation in thebioRxiv : the preprint server for biology · 2025Article
- Neuron-specific Agrin splicing by Nova RNA-binding proteins regulates conserved neuromuscular junction development in chordates.PLoS biology · 2025Article
- Synergic action of MicroRNAs and Wnts delivered by motor neuron EVs in promoting AChR clustering.Cell communication and signaling : CCS · 2025Article
- MuSK is a substrate for CaMK2β but this interaction is dispensable for MuSK activation in vivo.Scientific reports · 2025Article
- MuSK Regulates Neuromuscular Junction Nav1.4 Localization and Excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Gut-muscle axis crosstalk in age-related sarcopenia: mechanisms and therapeutic targets.Frontiers in microbiology · 2025Review
- Neuromuscular junction dysfunction in Lafora disease.Disease models & mechanisms · 2024Article
- A conserved RNA switch for acetylcholine receptor clustering at neuromuscular junctions in chordates.bioRxiv : the preprint server for biology · 2024Article
- The MuSK agonist antibody protects the neuromuscular junction and extends the lifespan in C9orf72-ALS mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Building, Breaking, and Repairing Neuromuscular Synapses.Cold Spring Harbor perspectives in biology · 2024Review
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Synapses are the fundamental units of neural circuits that enable complex behaviors. The neuromuscular junction (NMJ), a synapse formed between a motoneuron and a muscle fiber, has contributed greatly to understanding of the general principles of synaptogenesis as well as of neuromuscular disorders. NMJ formation requires neural agrin, a motoneuron-derived protein, which interacts with LRP4 (low-density lipoprotein receptor-related protein 4) to activate the receptor tyrosine kinase MuSK (muscle-specific kinase). However, little is known of how signals are transduced from agrin to MuSK. Here, we present the first crystal structure of an agrin-LRP4 complex, consisting of two agrin-LRP4 heterodimers. Formation of the initial binary complex requires the z8 loop that is specifically present in neuronal, but not muscle, agrin and that promotes the synergistic formation of the tetramer through two additional interfaces. We show that the tetrameric complex is essential for neuronal agrin-induced acetylcholine receptor (AChR) clustering. Collectively, these results provide new insight into the agrin-LRP4-MuSK signaling cascade and NMJ formation and represent a novel mechanism for activation of receptor tyrosine kinases.
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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.