title: Nitric oxide is a downstream mediator of agrin-induced acetylcholine receptor aggregation.
abstract: The synaptic basal lamina protein, agrin, is required for the formation of the neuromuscular junction. Agrin signals through a muscle-specific receptor tyrosine kinase (MuSK) initiating a cascade of events that lead to the aggregation of acetylcholine receptors (AChR) at the postsynaptic site. Another important synaptic signalling molecule is nitric oxide (NO), which is produced by the enzyme, nitric oxide synthase (NOS). We investigated the interaction between the agrin signalling cascade and the NO signalling cascade by treating cultured myotubes with agrin, NOS inhibitors, and NO donors. NOS inhibitors prevented agrin induced AChR aggregation and phosphorylation of the AChR beta subunit. Furthermore, NO donors induced AChR aggregation in the absence of agrin, as well as phosphorylation of the AChR beta subunit. These results demonstrate a role for NO as a downstream mediator of agrin induced AChR aggregation and AChR beta subunit phosphorylation at the neuromuscular junction.
authors.affiliation: Department of Anatomy and Cell Biology, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Jones
authors.forename: M J
authors.initials: MJ
authors.lastname: Werle
mesh_terms: D018171:Agrin / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D011950:Receptors, Cholinergic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D018171:Agrin; D004791:Enzyme Inhibitors; D006146:Guanidines; D020030:Nitric Oxide Donors; D011950:Receptors, Cholinergic; C110881:S-nitro-N-acetylpenicillamine; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D010396:Penicillamine; C004479:pimagedine