The extracellular region of Lrp4 is sufficient to mediate neuromuscular synapse formation
Article first published online: 28 OCT 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 240, Issue 12, pages 2626–2633, December 2011
How to Cite
Gomez, A. M. and Burden, S. J. (2011), The extracellular region of Lrp4 is sufficient to mediate neuromuscular synapse formation. Dev. Dyn., 240: 2626–2633. doi: 10.1002/dvdy.22772
- Issue published online: 9 NOV 2011
- Article first published online: 28 OCT 2011
- Accepted manuscript online: 17 OCT 2011 11:43AM EST
- Manuscript Accepted: 5 OCT 2011
- NIH. Grant Number: NS36193
- acetylcholine receptor;
- low-density lipoprotein-related receptor;
- skeletal muscle
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.