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The extracellular region of Lrp4 is sufficient to mediate neuromuscular synapse formation
Author(s) -
Gomez Andrea M.,
Burden Steven J.
Publication year - 2011
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22772
Subject(s) - agrin , biology , postsynaptic potential , neuromuscular junction , microbiology and biotechnology , intracellular , synapse , dystroglycan , acetylcholine receptor , motor endplate , neuroscience , receptor , biochemistry , extracellular matrix , laminin
Neuromuscular synapse formation requires an exchange of signals between motor neurons and muscle. Agrin, supplied by motor neurons, binds to Lrp4 in muscle, stimulating phosphorylation of MuSK and recruitment of a signaling complex essential for synapse‐specific transcription and anchoring of key proteins in the postsynaptic membrane. Lrp4, like the LDLR and other Lrp‐family members, contains an intracellular region with motifs that can regulate receptor trafficking, as well as assembly of an intracellular signaling complex. Here, we show that the intracellular region of Lrp4 is dispensable for Agrin to stimulate MuSK phosphorylation and clustering of acetylcholine receptors in cultured myotubes. Moreover, muscle‐selective expression of a Lrp4‐CD4 chimera, composed of the extracellular and transmembrane regions of Lrp4 and the intracellular region of CD4, rescues neuromuscular synapse formation and the neonatal lethality of lrp4 mutant mice, demonstrating that Lrp4, lacking the Lrp4 intracellular region, is sufficient for presynaptic and postsynaptic differentiation. Developmental Dynamics 240:2626–2633, 2011. © 2011 Wiley Periodicals, Inc.