Cell
Volume 132, Issue 1, 11 January 2008, Pages 125-136
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Article
A β-arrestin 2 Signaling Complex Mediates Lithium Action on Behavior

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Summary

Besides their role in desensitization, β-arrestin 1 and 2 promote the formation of signaling complexes allowing G protein-coupled receptors (GPCR) to signal independently from G proteins. Here we show that lithium, a pharmacological agent used for the management of psychiatric disorders such as bipolar disorder, schizophrenia, and depression, regulates Akt/glycogen synthase kinase 3 (GSK3) signaling and related behaviors in mice by disrupting a signaling complex composed of Akt, β-arrestin 2, and protein phosphatase 2A. When administered to β-arrestin 2 knockout mice, lithium fails to affect Akt/GSK3 signaling and induce behavioral changes associated with GSK3 inhibition as it does in normal animals. These results point toward a pharmacological approach to modulating GPCR function that affects the formation of β-arrestin-mediated signaling complexes.

MOLNEURO

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Present address: Department of Physiology and Anatomy, CRULR-Université Laval, Quebec City, Quebec, Canada.