AChR Clustering is Increased by Neuregulin

Abstract

In skeletal muscle development, agrin is released by the approaching motor neuron prior to innervation and the formation of the neuromuscular synapse. Agrin induces the clustering of existing acetylcholine receptors (AChRs) at the site of the future neuromuscular synapse through an agrin signaling pathway. Neuregulin is also released by the approaching motor neuron and induces the production of additional AChRs, especially at the nuclei near the future neuromuscular synapse. Our lab investigates myogenesis and neuromuscular synapse formation using the C2C12 myotube cell culture model. C2C12 myoblasts proliferate in growth medium, and then fuse into myotubes when switched to low‐serum differentiation medium (DM) for 72 hours. Myotubes are stimulated to cluster AChRs by the addition of agrin for the last 16 hours in DM. Our hypothesis was that neuregulin would increase AChR clustering in C2C12 myotubes as previously demonstrated in another cell line. Concentrations of agrin or neuregulin as low as 10 ng/ml was sufficient to increase AChR clustering. We conclude that AChR clustering in C2C12 myotubes is increased either by utilizing existing AChRs or the production of additional AChRs.Grant Funding Source: None