Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation

Haitao Wu, Yisheng Lu, Chengyong Shen, Neil Patel, Lin Gan, Wencheng Xiong, Lin Mei

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Neuromuscular junction (NMJ) formation requires precise interaction between motoneurons and muscle fibers. LRP4 is a receptor of agrin that is thought to act in cis to stimulate MuSK in muscle fibers for postsynaptic differentiation. Here we dissected the roles of LRP4 in muscle fibers and motoneurons in NMJ formation by cell-specific mutation. Studies of muscle-specific mutants suggest that LRP4 is involved in deciding where to form AChR clusters in muscle fibers, postsynaptic differentiation, and axon terminal development. LRP4 in HEK293 cells increased synapsin or SV2 puncta in contacting axons of cocultured neurons, suggesting a synaptogenic function. Analysis of LRP4 muscle and motoneuron double mutants and mechanistic studies suggest that NMJ formation may also be regulated by LRP4 in motoneurons, which could serve as agrin's receptor in trans to induce AChR clusters. These observations uncovered distinct roles of LRP4 in motoneurons and muscles in NMJ development.

Original languageEnglish (US)
Pages (from-to)94-107
Number of pages14
JournalNeuron
Volume75
Issue number1
DOIs
StatePublished - Jul 12 2012

ASJC Scopus subject areas

  • Neuroscience(all)

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    Wu, H., Lu, Y., Shen, C., Patel, N., Gan, L., Xiong, W., & Mei, L. (2012). Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation. Neuron, 75(1), 94-107. https://doi.org/10.1016/j.neuron.2012.04.033