The muscle protein Dok-7 is essential for neuromuscular synaptogenesis.
Okada K,
Inoue A,
Okada M,
Murata Y,
Kakuta S,
Jigami T,
Kubo S,
Shiraishi H,
Eguchi K,
Motomura M,
Akiyama T,
Iwakura Y,
Higuchi O,
Yamanashi Y.
Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
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.
PMID: 16794080 [PubMed - indexed for MEDLINE]