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PMID:19020093

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Citation

Henriquez, JP, Webb, A, Bence, M, Bildsoe, H, Sahores, M, Hughes, SM and Salinas, PC (2008) Wnt signaling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin. Proc. Natl. Acad. Sci. U.S.A. 105:18812-7

Abstract

Wnt proteins regulate the formation of central synapses by stimulating synaptic assembly, but their role at the vertebrate neuromuscular junction (NMJ) is unclear. Wnt3 is expressed by lateral motoneurons of the spinal cord during the period of motoneuron-muscle innervation. Using gain- and loss-of-function studies in the chick wing, we demonstrate that Wnt signaling is necessary for the formation of acetylcholine receptor (AChR) clusters without affecting muscle growth. Similarly, diaphragms from Dishevelled-1 mutant mice with deficiency in Wnt signaling exhibit defects in cluster distribution. In cultured myotubes, Wnt3 increases the number and size of AChR clusters induced by agrin, a nerve-derived signal critical for NMJ development. Wnt3 does not signal through the canonical Wnt pathway to induce cluster formation. Instead, Wnt3 induces the rapid formation of unstable AChR micro-clusters through activation of Rac1, which aggregate into large clusters only in the presence of agrin. Our data reveal a role for Wnts in post-synaptic assembly at the vertebrate NMJ by enhancing agrin function through Rac1 activation.

Links

PubMed PMC2585041 Online version:10.1073/pnas.0806300105

Keywords

Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Agrin/genetics; Agrin/metabolism; Animals; Cells, Cultured; Chick Embryo; Mice; Mice, Knockout; Muscle Fibers, Skeletal/metabolism; Neuromuscular Junction/physiology; Phosphoproteins/genetics; Phosphoproteins/metabolism; Receptors, Cholinergic/genetics; Receptors, Cholinergic/metabolism; Signal Transduction/physiology; Wnt Proteins/genetics; Wnt Proteins/metabolism; Wnt3 Protein; rac1 GTP-Binding Protein/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DVL1

acts_upstream_of_or_within

GO:0071340: skeletal muscle acetylcholine-gated channel clustering

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2137230

P

  • occurs_in:(CL:0000188)
  • occurs_in:(EMAPA:17701)

Seeded From UniProt

complete


See also

References

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