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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Beaulieu, J-M; Marion, S; Rodriguiz, RM; Medvedev, IO; Sotnikova, TD; Ghisi, V; Wetsel, WC; Lefkowitz, RJ; Gainetdinov, RR; Caron, MG

Published Date

  • January 11, 2008

Published In

Volume / Issue

  • 132 / 1

Start / End Page

  • 125 - 136

PubMed ID

  • 18191226

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2007.11.041

Language

  • eng

Conference Location

  • United States