Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse

Weichun Lin, Robert W. Burgess, Bertha Dominguez, Samuel L. Pfaff, Joshua R. Sanes and Kuo-Fen Lee ()
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Weichun Lin: The Salk Institute
Robert W. Burgess: Washington University Medical School
Bertha Dominguez: The Salk Institute
Samuel L. Pfaff: The Salk Institute
Joshua R. Sanes: Washington University Medical School
Kuo-Fen Lee: The Salk Institute

Nature, 2001, vol. 410, issue 6832, 1057-1064

Abstract: Abstract The development of chemical synapses is regulated by interactions between pre- and postsynaptic cells. At the vertebrate skeletal neuromuscular junction, the organization of an acetylcholine receptor (AChR)-rich postsynaptic apparatus has been well studied. Much evidence suggests that the nerve-derived protein agrin activates muscle-specific kinase (MuSK) to cluster AChRs through the synapse-specific cytoplasmic protein rapsyn. But how postsynaptic differentiation is initiated, or why most synapses are restricted to an ‘end-plate band’ in the middle of the muscle remains unknown. Here we have used genetic methods to address these issues. We report that the initial steps in postsynaptic differentiation and formation of an end-plate band require MuSK and rapsyn, but are not dependent on agrin or the presence of motor axons. In contrast, the subsequent stages of synaptic growth and maintenance require nerve-derived agrin, and a second nerve-derived signal that disperses ectopic postsynaptic apparatus.

Date: 2001
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DOI: 10.1038/35074025

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