LRP4 serves as a coreceptor of agrin

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Published on: May 5, 2020

Bin Zhang1, Shiwen Luo, Qiang Wang

  • 1Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA.

Neuron
|October 30, 2008
PubMed

Insights

Low-density lipoprotein receptor-related protein 4 (LRP4) acts as a crucial coreceptor for agrin, enabling neuromuscular junction formation. LRP4 is essential for MuSK signaling and acetylcholine receptor clustering in muscle cells.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Neuromuscular junction (NMJ) formation is vital for muscle function.
  • Agrin signaling through MuSK kinase is critical for NMJ development.
  • The precise mechanism of agrin-induced MuSK activation remained elusive.

Purpose of the Study:

  • To elucidate the role of LRP4 in agrin-induced signaling at the NMJ.
  • To investigate LRP4's interaction with MuSK and its function in acetylcholine receptor (AChR) clustering.
  • To identify LRP4 as a potential factor in muscular dystrophies.

Main Methods:

  • Investigated LRP4 expression in myotubes.
  • Assessed LRP4's binding to neuronal agrin.
  • Studied the impact of LRP4 suppression on agrin binding, MuSK phosphorylation, and AChR clustering.
  • Analyzed LRP4-MuSK complex formation and LRP4 tyrosine phosphorylation.

Main Results:

  • LRP4 is specifically expressed in myotubes and binds neuronal agrin.
  • LRP4 expression is necessary for agrin binding and MuSK signaling.
  • Suppression of LRP4 impairs agrin-induced MuSK phosphorylation and AChR clustering.
  • Agrin stimulation induces LRP4-MuSK complex formation and LRP4 tyrosine phosphorylation.

Conclusions:

  • LRP4 functions as a coreceptor essential for agrin-mediated MuSK signaling.
  • LRP4 is indispensable for proper NMJ formation, including AChR clustering.
  • LRP4 represents a potential therapeutic target for muscular dystrophies linked to mutations or autoimmunization.

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