A phosphatase cascade by which rewarding stimuli control nucleosomal response

Stipanovich, Alexandre, Valjent, Emmanuel, Matamales, Miriam, Nishi, Akinori, Ahn, Jung-Hyuck, Maroteaux, Matthieu, Bertran-Gonzalez, Jesus, Brami-Cherrier, Karen, Enslen, Hervé, Corbillé, Anne-Gaëlle, Filhol, Odile, Nairn, Angus C., Greengard, Paul, Hervé, Denis and Girault, Jean-Antoine (2008) A phosphatase cascade by which rewarding stimuli control nucleosomal response. Nature, 453 7197: 879-884. doi:10.1038/nature06994

Author Stipanovich, Alexandre
Valjent, Emmanuel
Matamales, Miriam
Nishi, Akinori
Ahn, Jung-Hyuck
Maroteaux, Matthieu
Bertran-Gonzalez, Jesus
Brami-Cherrier, Karen
Enslen, Hervé
Corbillé, Anne-Gaëlle
Filhol, Odile
Nairn, Angus C.
Greengard, Paul
Hervé, Denis
Girault, Jean-Antoine
Title A phosphatase cascade by which rewarding stimuli control nucleosomal response
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2008-06-12
Sub-type Article (original research)
DOI 10.1038/nature06994
Open Access Status
Volume 453
Issue 7197
Start page 879
End page 884
Total pages 7
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Dopamine orchestrates motor behaviour and reward-driven learning. Perturbations of dopamine signalling have been implicated in several neurological and psychiatric disorders, and in drug addiction. The actions of dopamine are mediated in part by the regulation of gene expression in the striatum, through mechanisms that are not fully understood. Here we show that drugs of abuse, as well as food reinforcement learning, promote the nuclear accumulation of 32-kDa dopamine-regulated and cyclic-AMP-regulated phosphoprotein (DARPP-32). This accumulation is mediated through a signalling cascade involving dopamine D1 receptors, cAMP-dependent activation of protein phosphatase-2A, dephosphorylation of DARPP-32 at Ser 97 and inhibition of its nuclear export. The nuclear accumulation of DARPP-32, a potent inhibitor of protein phosphatase-1, increases the phosphorylation of histone H3, an important component of nucleosomal response. Mutation of Ser 97 profoundly alters behavioural effects of drugs of abuse and decreases motivation for food, underlining the functional importance of this signalling cascade.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes A Methods page follows page 884 at the end of the article. 7 pages in total.

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 120 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 30 Jul 2014, 09:54:07 EST by J Bertran Gonzalez on behalf of Clem Jones Centre for Ageing Dementia Research