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Publication : Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation.

First Author  Wu H Year  2012
Journal  Neuron Volume  75
Issue  1 Pages  94-107
PubMed ID  22794264 Mgi Jnum  J:188352
Mgi Id  MGI:5440363 Doi  10.1016/j.neuron.2012.04.033
Citation  Wu H, et al. (2012) Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation. Neuron 75(1):94-107
abstractText  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.
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