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, Kuo Fen Lee

Research output: Contribution to journalArticle

397 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1057-1064
Number of pages8
JournalNature
Volume410
Issue number6832
DOIs
StatePublished - Apr 26 2001

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Agrin
Synapses
Muscles
Neuromuscular Junction
Cholinergic Receptors
Axons
Vertebrates
Proteins
Phosphotransferases
Maintenance
Growth
peripheral membrane protein 43K

ASJC Scopus subject areas

  • General

Cite this

Lin, W., Burgess, R. W., Dominguez, B., Pfaff, S. L., Sanes, J. R., & Lee, K. F. (2001). Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Nature, 410(6832), 1057-1064. https://doi.org/10.1038/35074025

Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. / Lin, Weichun; Burgess, Robert W.; Dominguez, Bertha; Pfaff, Samuel L.; Sanes, Joshua R.; Lee, Kuo Fen.

In: Nature, Vol. 410, No. 6832, 26.04.2001, p. 1057-1064.

Research output: Contribution to journalArticle

Lin, W, Burgess, RW, Dominguez, B, Pfaff, SL, Sanes, JR & Lee, KF 2001, 'Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse', Nature, vol. 410, no. 6832, pp. 1057-1064. https://doi.org/10.1038/35074025
Lin W, Burgess RW, Dominguez B, Pfaff SL, Sanes JR, Lee KF. Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Nature. 2001 Apr 26;410(6832):1057-1064. https://doi.org/10.1038/35074025
Lin, Weichun ; Burgess, Robert W. ; Dominguez, Bertha ; Pfaff, Samuel L. ; Sanes, Joshua R. ; Lee, Kuo Fen. / Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. In: Nature. 2001 ; Vol. 410, No. 6832. pp. 1057-1064.
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