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.
Pubmed ID: 16794080 RIS Download
Agrin | 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 | Muscle Denervation | Muscle Fibers, Skeletal | Muscle Proteins | Muscle, Skeletal | Mutation | Neuromuscular Junction | Phosphorylation | Protein Binding | Protein Structure, Tertiary | Receptor Aggregation | Receptor Protein-Tyrosine Kinases | Receptors, Cholinergic | Synapses | Synaptic Transmission