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.
Okada
Kumiko
K
Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Inoue
Akane
A
Okada
Momoko
M
Murata
Yoji
Y
Kakuta
Shigeru
S
Jigami
Takafumi
T
Kubo
Sachiko
S
Shiraishi
Hirokazu
H
Eguchi
Katsumi
K
Motomura
Masakatsu
M
Akiyama
Tetsu
T
Iwakura
Yoichiro
Y
Higuchi
Osamu
O
Yamanashi
Yuji
Y
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
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