Cited by 525Muscle Physiology and DisordersMyasthenia Gravis and ThymomaNicotinic Acetylcholine Receptors Study

LRP4 serves as a coreceptor of Agrin

Open access
Zhang, Bin, Luo, Shiwen, Wang, Qiang, Suzuki, Tatsuo, Xiong, Wen C., Mei, Lin·2008·Neuron

Abstract

Neuromuscular junction (NMJ) formation requires agrin, a factor released from motoneurons, and MuSK, a transmembrane tyrosine kinase that is activated by agrin. However, how signal is transduced from agrin to MuSK remains unclear. We report that LRP4, a low-density lipoprotein receptor (LDLR)-related protein, is expressed specifically in myotubes and binds to neuronal agrin. Its expression enables agrin binding and MuSK signaling in cells that otherwise do not respond to agrin. Suppression of LRP4 expression in muscle cells attenuates agrin binding, agrin-induced MuSK tyrosine phosphorylation, and AChR clustering. LRP4 also forms a complex with MuSK in a manner that is stimulated by agrin. Finally, we showed that LRP4 becomes tyrosine-phosphorylated in agrin-stimulated muscle cells. These observations indicate that LRP4 is a coreceptor of agrin that is necessary for MuSK signaling and AChR clustering and identify a potential target protein whose mutation and/or autoimmunization may cause muscular dystrophies.

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Crossref · 10.1016/j.neuron.2008.10.006

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  • At the neuromuscular junction, Lrp4, APP, and MuSK form a complex that prepatterns the muscle.

    “at the NMJ, Lrp4, APP and muscle-specific kinase (MuSK) form a complex to prepattern the muscle [88–90]”

    From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [90]

  • Agrin released from motor neurons signals through APP, MuSK, and Lrp4 to recruit nicotinic acetylcholine receptors.

    “Agrin is released from the motor neuron and signals through APP, MuSK and Lrp4 to recruit nicotinic acetylcholine receptors (AChRs).”

    From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [90]

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Authors
Zhang, B., Luo, S., Wang, Q., Suzuki, T., Xiong, W. C., & Mei, L.
Affiliations
  • Augusta University (US)
  • Shinshu University (JP)
Corresponding author
Mei, Lin
Venue
Neuron
Publisher
Elsevier BV
Published
2008-10
Volume
60
Issue
2
Pages
285-297
ISSN
0896-6273 (ISSN-L)
OpenAlex
W1991623532
Cited by
525
References
86
Citations by year
2026: 12 · 2025: 27 · 2024: 24 · 2023: 20 · 2022: 27 · 2021: 24 · 2020: 40 · 2019: 27 · 2018: 26 · 2017: 23 · 2016: 32 · 2015: 23 · 2014: 30 · 2013: 46 · 2012: 46
FWCI
13.32
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • Muscular Dystrophy Association
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Neurology › Myasthenia Gravis and Thymoma
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
LRP4, agrin, musk, neuromuscular junction formation, co-receptors, low density lipoprotein receptor-related protein, tyrosine phosphorylation, acetylcholine receptor clustering, myotubes, muscular dystrophy, autoimmunization
MeSH terms
Animals, Cell Line, Humans, Motor Neurons, Synaptic Transmission, Neuromuscular Junction, Phosphorylation, Protein Binding, Receptor Aggregation, Receptors, Cholinergic, Receptors, LDL, Synaptic Membranes, Tyrosine, Signal Transduction, Presynaptic Terminals, Agrin, Muscle Fibers, Skeletal, Receptor Protein-Tyrosine Kinases, LDL-Receptor Related Proteins, Mice

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