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

Full 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.

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Author information

Author/s: Okada, Kumiko (K); 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);

Affiliation: Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Science (New York, N.Y.) (Science), published in United States. (Language: eng)

Reference: 2006-Jun; vol 312 (issue 5781) : pp 1802-5

Dates: Created 2006/06/23; Completed 2006/07/17; Revised 2008/11/21;

PMID: 16794080, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - metabolism
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 - embryology; metabolism
Muscle Denervation

Muscle Denervation
Muscle Fibers, Skeletal - cytology; metabolism
Muscle Proteins - chemistry; genetics; metabolism
Muscle, Skeletal - embryology; innervation; metabolism
Mutation
Neuromuscular Junction - physiology
Phosphorylation
Protein Binding
Protein Structure, Tertiary
Receptor Aggregation
Receptor Protein-Tyrosine Kinases - genetics; metabolism
Receptors, Cholinergic - genetics; metabolism
Synapses - physiology
Synaptic Transmission

Associated Chemicals: Agrin (0) ; DOK7 protein, human (0) ; Dok-7 protein, mouse (0) ; Muscle Proteins (0) ; Receptors, Cholinergic (0) ; Receptor Protein-Tyrosine Kinases (EC 2.7.1.112) ; MUSK protein, human (EC 2.7.10.1) ; MuSK protein, mouse (EC 2.7.10.1)

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