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

Full 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.

Author information

Author/s: Misgeld, Thomas (T); Kummer, Terrance T (TT); Lichtman, Jeff W (JW); Sanes, Joshua R (JR);

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

Grants: T32 GM 07200-28 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2005-Aug; vol 102 (issue 31) : pp 11088-93

Dates: Created 2005/08/03; Completed 2005/09/20; Revised 2008/11/20;

PMID: 16043708, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Acetylcholine - deficiency; physiology
Agrin - deficiency; genetics; physiology
Animals
Carbachol - pharmacology
Cell Differentiation
Choline O-Acetyltransferase - deficiency; genetics; physiology
Female

Mice
Mice, Knockout
Models, Neurological
Neuromuscular Junction - drug effects; embryology; physiology
Neurotransmitter Agents - deficiency; pharmacology; physiology
Pregnancy
Synapses - drug effects; physiology

Associated Chemicals: Agrin (0) ; Neurotransmitter Agents (0) ; Carbachol (51-83-2) ; Acetylcholine (51-84-3) ; Choline O-Acetyltransferase (EC 2.3.1.6)

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