Muscle-derived neurotrophin-3 increases the aggregation of acetylcholine receptors in neuron-muscle co-cultures

Neurotrophins, a group of protein ligands that are structurally related to the prototype nerve growth factor (NGF), are prominently expressed in the skeletal muscle during the critical period of synapse formation. In the present study, we utilized a co-culture system of NG108-15 cells expressing the Trk receptors and C2C12 myotubes expressing the individual neurotrophins to examine whether these factors can act in a target-derived manner to influence the postsynaptic specializations. Our findings demonstrated that muscle-derived neurotrophin-3 (NT-3) has the unique ability to enhance the aggregation of acetylcholine receptors (AChRs) on the myotubes following co- culture with NG108-15 cells expressing TrkC. Taken together, our findings suggest that NT-3 can act as a retrograde factor to modulate the postsynaptic specializations.