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Publication : Neuregulin inhibits acetylcholine receptor aggregation in myotubes.

First Author  Trinidad JC Year  2004
Journal  J Biol Chem Volume  279
Issue  30 Pages  31622-8
PubMed ID  15155732 Mgi Jnum  J:91905
Mgi Id  MGI:3051094 Doi  10.1074/jbc.M400044200
Citation  Trinidad JC, et al. (2004) Neuregulin inhibits acetylcholine receptor aggregation in myotubes. J Biol Chem 279(30):31622-8
abstractText  The high local concentration of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction results from their aggregation by the agrin/MuSK signaling pathway and their synthetic up-regulation by the neuregulin/ErbB pathway. Here, we show a novel role for the neuregulin/ErbB pathway, the inhibition of AChR aggregation on the muscle surface. Treatment of C2C12 myotubes with the neuregulin epidermal growth factor domain decreased the number of both spontaneous and agrin-induced AChR clusters, in part by increasing the rate of cluster disassembly. Upon cluster disassembly, AChRs were internalized into caveolae (as identified by caveolin-3). Time-lapse microscopy revealed that individual AChR clusters fragmented into puncta, and application of neuregulin accelerated the rate at which AChR clusters decreased in area without affecting the density of AChRs remaining in individual clusters (as measured by the fluorescence intensity/unit area). We propose that this novel action of neuregulin regulates synaptic competition at the developing neuromuscular junction.
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