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Novel Modulation of Neuronal Nicotinic Acetylcholine Receptors by Association with the Endogenous Prototoxin lynx1

We previously identified lynx1 as a neuronal membrane molecule related to snake α-neurotoxins able to modulate nAChRs. Here, we show that lynx1 colocalizes with nAChRs on CNS neurons and physically associates with nAChRs. Single-channel recordings show that lynx1 promotes the largest of three curren...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2002-03, Vol.33 (6), p.893-903
Main Authors: Ibañez-Tallon, Inés, Miwa, Julie M, Wang, Hai-Long, Adams, Niels C, Crabtree, Gregg W, Sine, Steven M, Heintz, Nathaniel
Format: Article
Language:English
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Summary:We previously identified lynx1 as a neuronal membrane molecule related to snake α-neurotoxins able to modulate nAChRs. Here, we show that lynx1 colocalizes with nAChRs on CNS neurons and physically associates with nAChRs. Single-channel recordings show that lynx1 promotes the largest of three current amplitudes elicited by ACh through α 4β 2 nAChRs and that lynx1 enhances desensitization. Macroscopic recordings quantify the enhancement of desensitization onset by lynx1 and further show that it slows recovery from desensitization and increases the EC 50. These experiments establish that direct interaction of lynx1 with nAChRs can result in a novel type of functional modulation and suggest that prototoxins may play important roles in vivo by modulating functional properties of their cognate CNS receptors.
ISSN:0896-6273
1097-4199
DOI:10.1016/S0896-6273(02)00632-3