title: DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons.
abstract: 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.
authors.affiliation: 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.
authors.forename: Olivia
authors.initials: O
authors.lastname: Engmann
authors.affiliation: 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.
authors.forename: Albert
authors.initials: A
authors.lastname: Giralt
authors.affiliation: 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.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gervasi
authors.affiliation: 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.
authors.forename: Lucile
authors.initials: L
authors.lastname: Marion-Poll
authors.affiliation: 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.
authors.forename: Laila
authors.initials: L
authors.lastname: Gasmi
authors.affiliation: Inserm, U1036, CEA, 17 rue des Martyrs, Grenoble 38054, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Filhol
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, Connecticut 06511, USA.
authors.forename: Marina R
authors.initials: MR
authors.lastname: Picciotto
authors.affiliation: Upstate University Hospital, SUNY Upstate University, 5309 Weiskotten Hall, 766 Irving Avenue, Syracuse, New York 13210, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Gilligan
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, Connecticut 06511, USA.
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
authors.affiliation: 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.
authors.forename: Denis
authors.initials: D
authors.lastname: Hervé
authors.affiliation: 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.
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Girault
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D019556:COS Cells; D002110:Caffeine / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003042:Cocaine / Q000494:pharmacology; D049229:Dendritic Spines; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000187:drug effects / Q000378:metabolism*; D004777:Environment; D036681:Fluorescence Recovery After Photobleaching; D015151:Immunoblotting; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D000099291:Adducins
chemical_list: D002110:Caffeine; D002148:Calmodulin-Binding Proteins; D000697:Central Nervous System Stimulants; D003042:Cocaine; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D000099291:Adducins; C497929:Ppp1r1b protein, mouse; C497930:Ppp1r1b protein, rat