Structure of the neuromuscular junction: function and cooperative mechanisms in the synapse

Ann N Y Acad Sci. 2012 Dec;1274:14-23. doi: 10.1111/j.1749-6632.2012.06784.x.


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.

Publication types

  • Review

MeSH terms

  • Agrin / metabolism
  • Humans
  • Lambert-Eaton Myasthenic Syndrome / metabolism
  • Myasthenia Gravis / metabolism*
  • Neuromuscular Junction / metabolism*
  • Protein Structure, Tertiary
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Cholinergic / genetics
  • Receptors, Cholinergic / metabolism
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Signal Transduction
  • Synapses / metabolism*


  • Agrin
  • Receptors, Cholinergic
  • Ryanodine Receptor Calcium Release Channel
  • MUSK protein, human
  • Receptor Protein-Tyrosine Kinases