Publication Date:
2006-06-24
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okada, Kumiko -- Inoue, Akane -- Okada, Momoko -- Murata, Yoji -- Kakuta, Shigeru -- Jigami, Takafumi -- Kubo, Sachiko -- Shiraishi, Hirokazu -- Eguchi, Katsumi -- Motomura, Masakatsu -- Akiyama, Tetsu -- Iwakura, Yoichiro -- Higuchi, Osamu -- Yamanashi, Yuji -- New York, N.Y. -- Science. 2006 Jun 23;312(5781):1802-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16794080" target="_blank"〉PubMed〈/a〉
Keywords:
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 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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
