ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
LRP4 is critical for neuromuscular junction maintenance.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 149 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
- AGRN-, LRP4-, MUSK-Related CMS: Clinical, Neurophysiological, Morphological, Genetic and Pathological Mechanisms.Muscle & nerve · 2026Review
- Convergent Functional Genomic Evolution Underlying Repeated Freshwater Colonization in Cetaceans.Journal of molecular evolution · 2026Article
- Favorable outcome of engraftment of custom designed RADA16-I based hydrogels functionalized with SDF1 or IL4 mimicking peptides to injured or dystrophic muscles.Scientific reports · 2026Article
- Integrative proteogenomic analyses identify plasma proteins that impact the risk of ischemic stroke.Communications medicine · 2026Article
- Monoclonal antibody passive experimental autoimmune myasthenia gravis: current progress and future directions.Cell & bioscience · 2026Review
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Specific non-myogenic mesenchymal cells contribute to rotator cuff tear myosteatosis and fibrosis revealing novel therapeutic options.bioRxiv : the preprint server for biology · 2026Article
- Article
- New Insights into Neuromuscular Junction Biology: Evidence from Human and Animal Research.International journal of molecular sciences · 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
- Optimization of Induction Protocols for Experimental Autoimmune Myasthenia Gravis.International journal of molecular sciences · 2025Article
- Alternative Treatments to Exercise for the Attenuation of Disuse-Induced Skeletal Muscle Atrophy in Rats.Muscles (Basel, Switzerland) · 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
- Neuronal LRP4 directs the development, maturation and cytoskeletal organization of Drosophila peripheral synapses.Development (Cambridge, England) · 2024Article
- Agrin-Lrp4 pathway in hippocampal astrocytes restrains development of temporal lobe epilepsy through adenosine signaling.Cell & bioscience · 2024Article
- Functional Signature of LRP4 Antibodies in Myasthenia Gravis.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Deficiency of skeletal muscle Agrin contributes to the pathogenesis of age-related sarcopenia in mice.Cell death & disease · 2024Article
- Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes.Nature communications · 2024Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neuromuscular junction (NMJ) is a synapse between motor neurons and skeletal muscle fibers, and is critical for control of muscle contraction. Its formation requires neuronal agrin that acts by binding to LRP4 to stimulate MuSK. Mutations have been identified in agrin, MuSK, and LRP4 in patients with congenital myasthenic syndrome, and patients with myasthenia gravis develop antibodies against agrin, LRP4, and MuSK. However, it remains unclear whether the agrin signaling pathway is critical for NMJ maintenance because null mutation of any of the three genes is perinatal lethal. In this study, we generated imKO mice, a mutant strain whose LRP4 gene can be deleted in muscles by doxycycline (Dox) treatment. Ablation of the LRP4 gene in adult muscle enabled studies of its role in NMJ maintenance. We demonstrate that Dox treatment of P30 mice reduced muscle strength and compound muscle action potentials. AChR clusters became fragmented with diminished junctional folds and synaptic vesicles. The amplitude and frequency of miniature endplate potentials were reduced, indicating impaired neuromuscular transmission and providing cellular mechanisms of adult LRP4 deficiency. We showed that LRP4 ablation led to the loss of synaptic agrin and the 90 kDa fragments, which occurred ahead of other prejunctional and postjunctional components, suggesting that LRP4 may regulate the stability of synaptic agrin. These observations demonstrate that LRP4 is essential for maintaining the structural and functional integrity of the NMJ and that loss of muscle LRP4 in adulthood alone is sufficient to cause myasthenic symptoms.
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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.