DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons.

Autor: Engmann O; Inserm UMR-S 839, Paris 75005, France.; Sorbonne Universités, UPMC, Université Paris 06, Paris 75005, France.; Institut du Fer à Moulin, 17 rue du Fer à Moulin, Paris 75005, France., Giralt A; Inserm UMR-S 839, Paris 75005, France.; Sorbonne Universités, UPMC, Université Paris 06, Paris 75005, France.; Institut du Fer à Moulin, 17 rue du Fer à Moulin, Paris 75005, France., Gervasi N; Inserm UMR-S 839, Paris 75005, France.; Sorbonne Universités, UPMC, Université Paris 06, Paris 75005, France.; Institut du Fer à Moulin, 17 rue du Fer à Moulin, Paris 75005, France., Marion-Poll L; Inserm UMR-S 839, Paris 75005, France.; Sorbonne Universités, UPMC, Université Paris 06, Paris 75005, France.; Institut du Fer à Moulin, 17 rue du Fer à Moulin, Paris 75005, France., Gasmi L; Inserm UMR-S 839, Paris 75005, France.; Sorbonne Universités, UPMC, Université Paris 06, Paris 75005, France.; Institut du Fer à Moulin, 17 rue du Fer à Moulin, Paris 75005, France., Filhol O; Inserm, U1036, CEA, 17 rue des Martyrs, Grenoble 38054, France., Picciotto MR; Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, Connecticut 06511, USA., Gilligan D; Upstate University Hospital, SUNY Upstate University, 5309 Weiskotten Hall, 766 Irving Avenue, Syracuse, New York 13210, USA., Greengard P; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA., Nairn AC; Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, Connecticut 06511, USA., Hervé D; Inserm UMR-S 839, Paris 75005, France.; Sorbonne Universités, UPMC, Université Paris 06, Paris 75005, France.; Institut du Fer à Moulin, 17 rue du Fer à Moulin, Paris 75005, France., Girault JA; Inserm UMR-S 839, Paris 75005, France.; Sorbonne Universités, UPMC, Université Paris 06, Paris 75005, France.; Institut du Fer à Moulin, 17 rue du Fer à Moulin, Paris 75005, France.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2015 Dec 07; Vol. 6, pp. 10099. Date of Electronic Publication: 2015 Dec 07.
DOI: 10.1038/ncomms10099
Abstrakt: Environmental enrichment has multiple effects on behaviour, including modification of responses to psychostimulant drugs mediated by striatal neurons. However, the underlying molecular and cellular mechanisms are not known. Here we show that DARPP-32, a hub signalling protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin filaments' fast-growing ends and regulate synaptic stability. DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP-32 Ser97 phosphorylation. Phospho-Thr75-DARPP-32 facilitates β-adducin Ser713 phosphorylation through inhibition of a cAMP-dependent protein kinase/phosphatase-2A cascade. Caffeine or 24-h exposure to a novel enriched environment increases adducin phosphorylation in WT, but not T75A mutant mice. This cascade is implicated in the effects of brief exposure to novel enriched environment on dendritic spines in nucleus accumbens and cocaine locomotor response. Our results suggest a molecular pathway by which environmental changes may rapidly alter responsiveness of striatal neurons involved in the reward system.
Databáze: MEDLINE
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