Work

Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter

Year: 2005

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0504806102

Authors: Thomas Misgeld, Terrance T. Kummer, Jeff W. Lichtman, Joshua R. Sanes

Institutions: Harvard University, Washington University in St. Louis

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

Open Access status: green

Funders: Deutsche Forschungsgemeinschaft, National Institutes of Health, National Institute of General Medical Sciences

Awards: G304139194, G865654374, G9000167305, G9000224954