Editors' ChoiceNeuroscience

Dok-7 Building the Synapse

Science's STKE  27 Jun 2006:
Vol. 2006, Issue 341, pp. tw216
DOI: 10.1126/stke.3412006tw216

The synapse between motor neurons and skeletal muscles forms during development when the neuron contacts the muscle and secretes a protein called agrin. Agrin, in turn, causes phosphorylation of a muscle-specific receptor kinase, MuSK, ultimately resulting in clustering of acetylcholine receptors on the muscle membrane at the site of nerve contact. Okada et al. now describe Dok-7, a protein that can bypass the requirement for agrin and that is required for MuSK activation, binding to and activating MuSK through a PTB domain. Mice engineered to lack Dok-7 do not form clusters of neurotransmitter receptors, and a mutant form of Dok-7 found in patients with congenital myasthenic syndrome prevents normal receptor clustering and junction formation. Thus, Dok-7 is a MuSK binding protein required for the formation of the postsynaptic side of the neuromuscular junction.

K. Okada, A. Inoue, M. Okada, Y. Murata, S. Kakuta, T. Jigami, S. Kubo, H. Shiraishi, K. Eguchi, M. Motomura, T. Akiyama, Y. Iwakura, O. Higuchi, Y. Yamanashi, The muscle protein Dok-7 is essential for neuromuscular synaptogenesis. Science 312, 1802-1805 (2006). [Abstract] [Full Text]