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

Publication ,  Journal Article
Beaulieu, J-M; Marion, S; Rodriguiz, RM; Medvedev, IO; Sotnikova, TD; Ghisi, V; Wetsel, WC; Lefkowitz, RJ; Gainetdinov, RR; Caron, MG
Published in: Cell
January 11, 2008
Published version (DOI) Link to item

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.

Duke Scholars

Robert J. Lefkowitz
Author Robert J. Lefkowitz Medicine, Cardiology
William Christopher Wetsel
Author William Christopher Wetsel Psychiatry & Behavioral Sciences, Behavioral Medicine & Neur ...
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Published In

Cell

DOI

10.1016/j.cell.2007.11.041

ISSN

0092-8674

Publication Date

January 11, 2008

Volume

132

Issue

1

Start / End Page

125 / 136

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • beta-Arrestin 1
  • Signal Transduction
  • Receptors, G-Protein-Coupled
  • Proto-Oncogene Proteins c-akt
  • Protein Phosphatase 2
  • Motor Activity
  • Mood Disorders
  • Mice, Knockout
 

Citation

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Chicago
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MLA
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Beaulieu, J.-M., Marion, S., Rodriguiz, R. M., Medvedev, I. O., Sotnikova, T. D., Ghisi, V., … Caron, M. G. (2008). A beta-arrestin 2 signaling complex mediates lithium action on behavior. Cell, 132(1), 125–136. https://doi.org/10.1016/j.cell.2007.11.041
Beaulieu, Jean-Martin, Sébastien Marion, Ramona M. Rodriguiz, Ivan O. Medvedev, Tatyana D. Sotnikova, Valentina Ghisi, William C. Wetsel, Robert J. Lefkowitz, Raul R. Gainetdinov, and Marc G. Caron. “A beta-arrestin 2 signaling complex mediates lithium action on behavior.” Cell 132, no. 1 (January 11, 2008): 125–36. https://doi.org/10.1016/j.cell.2007.11.041.
Beaulieu J-M, Marion S, Rodriguiz RM, Medvedev IO, Sotnikova TD, Ghisi V, et al. A beta-arrestin 2 signaling complex mediates lithium action on behavior. Cell. 2008 Jan 11;132(1):125–36.
Beaulieu, Jean-Martin, et al. “A beta-arrestin 2 signaling complex mediates lithium action on behavior.” Cell, vol. 132, no. 1, Jan. 2008, pp. 125–36. Pubmed, doi:10.1016/j.cell.2007.11.041.
Beaulieu J-M, Marion S, Rodriguiz RM, Medvedev IO, Sotnikova TD, Ghisi V, Wetsel WC, Lefkowitz RJ, Gainetdinov RR, Caron MG. A beta-arrestin 2 signaling complex mediates lithium action on behavior. Cell. 2008 Jan 11;132(1):125–136.
Journal cover image

Published In

Cell

DOI

10.1016/j.cell.2007.11.041

ISSN

0092-8674

Publication Date

January 11, 2008

Volume

132

Issue

1

Start / End Page

125 / 136

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Arrestin 2
  • beta-Arrestin 1
  • Signal Transduction
  • Receptors, G-Protein-Coupled
  • Proto-Oncogene Proteins c-akt
  • Protein Phosphatase 2
  • Motor Activity
  • Mood Disorders
  • Mice, Knockout