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The muscle protein Dok-7 is essential for neuromuscular synaptogenesis.

The formation of the neuromuscular synapse requires muscle-specific receptor kinase (MuSK) to orchestrate postsynaptic differentiation, including the clustering of receptors for the neurotransmitter acetylcholine. Upon innervation, neural agrin activates MuSK to establish the postsynaptic apparatus, although agrin-independent formation of neuromuscular synapses can also occur experimentally in the absence of neurotransmission. Dok-7, a MuSK-interacting cytoplasmic protein, is essential for MuSK activation in cultured myotubes; in particular, the Dok-7 phosphotyrosine-binding domain and its target in MuSK are indispensable. Mice lacking Dok-7 formed neither acetylcholine receptor clusters nor neuromuscular synapses. Thus, Dok-7 is essential for neuromuscular synaptogenesis through its interaction with MuSK.

Pubmed ID: 16794080


  • Okada K
  • Inoue A
  • Okada M
  • Murata Y
  • Kakuta S
  • Jigami T
  • Kubo S
  • Shiraishi H
  • Eguchi K
  • Motomura M
  • Akiyama T
  • Iwakura Y
  • Higuchi O
  • Yamanashi Y


Science (New York, N.Y.)

Publication Data

June 23, 2006

Associated Grants


Mesh Terms

  • Agrin
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Differentiation
  • Cell Line
  • Down-Regulation
  • Enzyme Activation
  • Humans
  • In Situ Hybridization
  • Mice
  • Molecular Sequence Data
  • Motor Endplate
  • Muscle Denervation
  • Muscle Fibers, Skeletal
  • Muscle Proteins
  • Muscle, Skeletal
  • Mutation
  • Neuromuscular Junction
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptor Aggregation
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Cholinergic
  • Synapses
  • Synaptic Transmission