A role for acetylcholine receptors in their own aggregation on muscle cells.
Both neurotrophic factors and activity regulate synaptogenesis. At neuromuscular synapses, the neural factor agrin released from motor neuron terminals stimulates postsynaptic specialization by way of the muscle specific kinase MuSK. In addition, activity through acetylcholine receptors (AChRs) has been implicated in the stabilization of pre- and postsynaptic contacts on muscle at various stages of development. We show here that activation of AChRs with specific concentrations of nicotine is sufficient to induce AChR aggregation and that this induction requires the function of L-type calcium channels (L-CaChs). Furthermore, AChR function is required for agrin induced AChR aggregation in C2 muscle cells. The same concentrations of nicotine did not induce observable tyrosine phosphorylation on either MuSK or the AChR beta subunit, suggesting significant differences between the mechanisms of agrin and activity induced aggregation. The AChR/L-CaCh pathway provides a mechanism by which neuromuscular signal transmission can act in concert with the agrin-MuSK signaling cascade to regulate NMJ formation.
Milholland
Rebecca B R
RB
Department of Cell Biology and Anatomy, University of Arizona Health Sciences Center, Tucson, Arizona 85724-5044, USA.
Gordon
Herman
H
D018171:Agrin / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D003472:Curare / Q000494:pharmacology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D018171:Agrin; D020746:Calcium Channels, L-Type; D021122:Protein Subunits; D011950:Receptors, Cholinergic; D019000:Phosphotyrosine; D009538:Nicotine; D003472:Curare; C475048:MuSK protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D009543:Nifedipine