title: The muscle protein Dok-7 is essential for neuromuscular synaptogenesis.
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.
authors.affiliation: Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Okada
authors.forename: Akane
authors.initials: A
authors.lastname: Inoue
authors.forename: Momoko
authors.initials: M
authors.lastname: Okada
authors.forename: Yoji
authors.initials: Y
authors.lastname: Murata
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kakuta
authors.forename: Takafumi
authors.initials: T
authors.lastname: Jigami
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kubo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shiraishi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Motomura
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akiyama
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Osamu
authors.initials: O
authors.lastname: Higuchi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamanashi
mesh_terms: D018171:Agrin / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D004789:Enzyme Activation; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009045:Motor Endplate / Q000196:embryology / Q000378:metabolism; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000196:embryology / Q000294:innervation* / Q000378:metabolism; D009154:Mutation; D009469:Neuromuscular Junction / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011940:Receptor Aggregation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D018171:Agrin; C511692:DOK7 protein, human; C511694:Dok-7 protein, mouse; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; C511695:MuSK protein, mouse; D020794:Receptor Protein-Tyrosine Kinases