Wnt proteins regulate acetylcholine receptor clustering in muscle cells

Bin Zhang, Chuan Liang, Ryan Bates, Yiming Yin, Wen Cheng Xiong, Lin Mei

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Background. The neuromuscular junction (NMJ) is a cholinergic synapse that rapidly conveys signals from motoneurons to muscle cells and exhibits a high degree of subcellular specialization characteristic of chemical synapses. NMJ formation requires agrin and its coreceptors LRP4 and MuSK. Increasing evidence indicates that Wnt signaling regulates NMJ formation in Drosophila, C. elegans and zebrafish. Results. In the study we systematically studied the effect of all 19 different Wnts in mammals on acetylcholine receptor (AChR) cluster formation. We identified five Wnts (Wnt9a, Wnt9b, Wnt10b, Wnt11, and Wnt16) that are able to stimulate AChR clustering, of which Wnt9a and Wnt11 are expressed abundantly in developing muscles. Using Wnt9a and Wnt11 as example, we demonstrated that Wnt induction of AChR clusters was dose-dependent and non-additive to that of agrin, suggesting that Wnts may act via similar pathways to induce AChR clusters. We provide evidence that Wnt9a and Wnt11 bind directly to the extracellular domain of MuSK, to induce MuSK dimerization and subsequent tyrosine phosphorylation of the kinase. In addition, Wnt-induced AChR clustering requires LRP4. Conclusions. These results identify Wnts as new players in AChR cluster formation, which act in a manner that requires both MuSK and LRP4, revealing a novel function of LRP4.

Original languageEnglish (US)
Article number7
JournalMolecular Brain
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • AChR clustering
  • muscle cells
  • neuromuscular junction
  • synapse formation
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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