ArticleNature2012
Lrp4 is a retrograde signal for presynaptic differentiation at neuromuscular synapses.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
112 citing papers in PubMed, 196 citations in OpenAlex.
- First-in-Human Dose Selection and Safety, Tolerability, Pharmacokinetics, and Immunogenicity of the Muscle-Specific Kinase Agonist Adimanebart (ARGX-119).Journal of clinical pharmacology · 2026Trial
- MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- NMJ-associated transcriptomic remodeling correlates with disease severity in juvenile dermatomyositis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Muscle-Specific Kinase Signaling and Its Therapeutic Potential.Muscle & nerve · 2026Review
- Review
- Neuromuscular junction formation by compartmentalized culture using human iPS cell-derived motor neurons and skeletal muscle cells.Frontiers in neural circuits · 2026Article
- The neuromuscular junction: a critical component of functional recovery after peripheral nerve injury.Frontiers in surgery · 2026Review
- Galactose treatment rescues neuromuscular junction transmission in glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) deficient mice.Human molecular genetics · 2025Article
- Harnessing synaptic vesicle release and recycling with antibody shuttle for targeted delivery of therapeutics to neurons.Molecular therapy. Methods & clinical development · 2025Article
- Intracellular protein-lipid interactions drive presynaptic assembly prior to neurexin recruitment.Neuron · 2025Article
- Patient-specific therapeutic benefit of MuSK agonist antibody ARGX-119 in MuSK myasthenia gravis passive transfer models.iScience · 2025Article
- Neurochemical and Morphological Comparisons of Motor Nerve Organoids and Spinal-Cord Explants.ACS chemical neuroscience · 2025Article
- Agonist antibody to MuSK protects mice from MuSK myasthenia gravis.Proceedings of the National Academy of Sciences of the United States of America · 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
- Building, Breaking, and Repairing Neuromuscular Synapses.Cold Spring Harbor perspectives in biology · 2024Review
- Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Calcitriol ameliorates motor deficits and prolongs survival of Chrne-deficient mouse, a model for congenital myasthenic syndrome, by inducing Rspo2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- A clinical perspective on muscle specific kinase antibody positive myasthenia gravis.Frontiers in immunology · 2024Review
- Neuronal LRP4 directs the development, maturation, and cytoskeletal organization of peripheral synapses.bioRxiv : the preprint server for biology · 2023Article
52 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
3 authors at 1 institution in 1 country.
Funding
Abstract
Motor axons receive retrograde signals from skeletal muscle that are essential for the differentiation and stabilization of motor nerve terminals. Identification of these retrograde signals has proved elusive, but their production by muscle depends on the receptor tyrosine kinase, MuSK (muscle, skeletal receptor tyrosine-protein kinase), and Lrp4 (low-density lipoprotein receptor (LDLR)-related protein 4), an LDLR family member that forms a complex with MuSK, binds neural agrin and stimulates MuSK kinase activity. Here we show that Lrp4 also functions as a direct muscle-derived retrograde signal for early steps in presynaptic differentiation. We demonstrate that Lrp4 is necessary, independent of MuSK activation, for presynaptic differentiation in vivo, and we show that Lrp4 binds to motor axons and induces clustering of synaptic-vesicle and active-zone proteins. Thus, Lrp4 acts bidirectionally and coordinates synapse formation by binding agrin, activating MuSK and stimulating postsynaptic differentiation, and functioning in turn as a muscle-derived retrograde signal that is necessary and sufficient for presynaptic differentiation.
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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.