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Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter

By Thomas Misgeld, Terrance T. Kummer, Jeff W. Lichtman and Joshua R. Sanes

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

Topics: Biological Sciences
Publisher: National Academy of Sciences
Year: 2005
DOI identifier: 10.1073/pnas.0504806102
OAI identifier: oai:pubmedcentral.nih.gov:1182450
Provided by: PubMed Central
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