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Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11088-93. Epub 2005 Jul 25.

Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter.

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1
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.

Abstract

Synaptic organizing molecules and neurotransmission regulate synapse development. Here, we use the skeletal neuromuscular junction to assess the interdependence of effects evoked by an essential synaptic organizing protein, agrin, and the neuromuscular transmitter, acetylcholine (ACh). Mice lacking agrin fail to maintain neuromuscular junctions, whereas neuromuscular synapses differentiate extensively in the absence of ACh. We now demonstrate that agrin's action in vivo depends critically on cholinergic neurotransmission. Using double-mutant mice, we show that synapses do form in the absence of agrin provided that ACh is also absent. We provide evidence that ACh destabilizes nascent postsynaptic sites, and that one major physiological role of agrin is to counteract this "antisynaptogenic" influence. Similar interactions between neurotransmitters and synaptic organizing molecules may operate at synapses in the central nervous system.

PMID:
16043708
PMCID:
PMC1182450
DOI:
10.1073/pnas.0504806102
[Indexed for MEDLINE]
Free PMC Article
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