LRP4 Serves as a Coreceptor of Agrin

Bin Zhang, Shiwen Luo, Qiang Wang, Tatsuo Suzuki, Wen C. Xiong, Lin Mei

Research output: Contribution to journalArticle

347 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)285-297
Number of pages13
JournalNeuron
Volume60
Issue number2
DOIs
StatePublished - Oct 23 2008

Keywords

  • CELLBIO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Zhang, B., Luo, S., Wang, Q., Suzuki, T., Xiong, W. C., & Mei, L. (2008). LRP4 Serves as a Coreceptor of Agrin. Neuron, 60(2), 285-297. https://doi.org/10.1016/j.neuron.2008.10.006