title: Structure of the neuromuscular junction: function and cooperative mechanisms in the synapse.
abstract: As an overview of the structure of the neuromuscular junction, three items are described focusing on cooperative mechanisms involving the synapse and leading to muscle contraction: (1) presynaptic acetylcholine release regulated by vesicle cycling (exocytosis and endocytosis); the fast-mode of endocytosis requires a large influx of external Ca(2+) and is promoted by the activation of G protein-coupled receptors and receptor tyrosine kinases; (2) postsynaptic acetylcholine receptor clustering mediated by the muscle-specific, Dok7-stimulated tyrosine kinase (MuSK) through two signaling mechanisms: one via agrin-Lrp4-MuSK (Ig1/2 domains) and the second via Wnt-MuSK (Frizzled-like cysteine-rich domain)-adaptor Dishevelled; Wnts/MuSK and Lrp4 direct a retrograde signal to presynaptic differentiation; (3) muscle contractile machinery regulated by Ca(2+) -release and Ca(2+) -influx channels, including the depolarization-activated ryanodine receptor-1 and the receptor- and/or store-operated transient receptor potential canonical. The first mechanism is dysfunctional in Lambert-Eaton myasthenic syndrome, the second in anti-acetylcholine receptor-negative myasthenia gravis (MG), and the third in thymoma-associated MG.
authors.affiliation: Neurological Center, Kanazawa-Nishi Hospital, Japan. m-takamori@vanilla.ocn.ne.jp
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takamori
mesh_terms: D018171:Agrin / Q000378:metabolism; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000378:metabolism; D009157:Myasthenia Gravis / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*
chemical_list: D018171:Agrin; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases