Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Agrin / metabolism
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Cell Differentiation
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Cell Line
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Down-Regulation
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Enzyme Activation
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Humans
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In Situ Hybridization
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Mice
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Molecular Sequence Data
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Motor Endplate / embryology
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Motor Endplate / metabolism
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Muscle Denervation
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Muscle Fibers, Skeletal / cytology
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Muscle Fibers, Skeletal / metabolism
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Muscle Proteins / chemistry
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Muscle, Skeletal / embryology
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Muscle, Skeletal / innervation*
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Muscle, Skeletal / metabolism
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Mutation
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Neuromuscular Junction / physiology*
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Phosphorylation
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Protein Binding
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Protein Structure, Tertiary
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Receptor Aggregation
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptors, Cholinergic / genetics
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Receptors, Cholinergic / metabolism*
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Synapses / physiology*
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Synaptic Transmission
Substances
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Agrin
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DOK7 protein, human
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Dok-7 protein, mouse
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Muscle Proteins
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Receptors, Cholinergic
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MUSK protein, human
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MuSK protein, mouse
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Receptor Protein-Tyrosine Kinases