A phosphatase cascade by which rewarding stimuli control nucleosomal response.

Nature (2008-05-23)
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
RESUMEN

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.

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Sigma-Aldrich
Poly-L-lysine solution, 0.01%, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Poly-L-lysine solution, 0.1 % (w/v) in H2O
Sigma-Aldrich
Poly-L-lysine solution, mol wt 150,000-300,000, 0.01%, sterile-filtered, BioReagent, suitable for cell culture