A phosphatase cascade by which rewarding stimuli control nucleosomal response

Alexandre Stipanovich, Emmanuel Valjent, Miriam Matamales, Akinori Nishi, Jung Hyuck Ahn, Matthieu Maroteaux, Jesus Bertran-Gonzalez, Karen Brami-Cherrier, Hervé Enslen, Anne Gaëlle Corbillé, Odile Filhol, Angus C. Nairn, Paul Greengard, Denis Hervé, Jean Antoine Girault

Research output: Contribution to journalArticlepeer-review

190 Scopus citations


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.

Original languageEnglish
Pages (from-to)879-884
Number of pages6
Issue number7197
StatePublished - 12 Jun 2008


Dive into the research topics of 'A phosphatase cascade by which rewarding stimuli control nucleosomal response'. Together they form a unique fingerprint.

Cite this