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. 2008 Jan 11;132(1):125-36.
doi: 10.1016/j.cell.2007.11.041.

A beta-arrestin 2 signaling complex mediates lithium action on behavior

Jean-Martin Beaulieu  1 , Sébastien Marion, Ramona M Rodriguiz, Ivan O Medvedev, Tatyana D Sotnikova, Valentina Ghisi, William C Wetsel, Robert J Lefkowitz, Raul R Gainetdinov, Marc G Caron
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Free article

A beta-arrestin 2 signaling complex mediates lithium action on behavior

Jean-Martin Beaulieu et al. Cell. .
Free article

Abstract

Besides their role in desensitization, beta-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, beta-arrestin 2, and protein phosphatase 2A. When administered to beta-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 beta-arrestin-mediated signaling complexes.

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