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

Olivia Engmann; Albert Giralt; Nicolas Gervasi; Lucile Marion-Poll; Laila Gasmi; Odile Filhol; Marina R Picciotto; Diana Gilligan; Paul Greengard; Angus C Nairn; Denis Hervé; Jean-Antoine Girault

doi:10.1038/ncomms10099

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

Nat Commun. 2015 Dec 7:6:10099. doi: 10.1038/ncomms10099.

Authors

Olivia Engmann^{1

2

3}, Albert Giralt^{1

2

3}, Nicolas Gervasi^{1

2

3}, Lucile Marion-Poll^{1

2

3}, Laila Gasmi^{1

2

3}, Odile Filhol⁴, Marina R Picciotto⁵, Diana Gilligan⁶, Paul Greengard⁷, Angus C Nairn⁵, Denis Hervé^{1

2

3}, Jean-Antoine Girault^{1

2

3}

Affiliations

¹ Inserm UMR-S 839, Paris 75005, France.
² Sorbonne Universités, UPMC, Université Paris 06, Paris 75005, France.
³ Institut du Fer à Moulin, 17 rue du Fer à Moulin, Paris 75005, France.
⁴ Inserm, U1036, CEA, 17 rue des Martyrs, Grenoble 38054, France.
⁵ Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, Connecticut 06511, USA.
⁶ Upstate University Hospital, SUNY Upstate University, 5309 Weiskotten Hall, 766 Irving Avenue, Syracuse, New York 13210, USA.
⁷ Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Behavior, Animal / drug effects
Behavior, Animal / physiology*
Brain / cytology
Brain / metabolism
COS Cells
Caffeine / pharmacology
Calmodulin-Binding Proteins / drug effects
Calmodulin-Binding Proteins / metabolism*
Central Nervous System Stimulants / pharmacology
Chlorocebus aethiops
Cocaine / pharmacology
Dendritic Spines
Dopamine and cAMP-Regulated Phosphoprotein 32 / drug effects
Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism*
Environment*
Fluorescence Recovery After Photobleaching
Immunoblotting
Immunohistochemistry
In Vitro Techniques
Mass Spectrometry
Mice
Mice, Inbred C57BL
Mutation
Neostriatum / cytology
Neostriatum / drug effects
Neostriatum / metabolism*
Neurons / cytology
Neurons / metabolism*
Nucleus Accumbens / cytology
Nucleus Accumbens / drug effects
Nucleus Accumbens / metabolism
Phosphorylation / drug effects
Rats
Rats, Sprague-Dawley
Reward

Substances

Calmodulin-Binding Proteins
Central Nervous System Stimulants
Dopamine and cAMP-Regulated Phosphoprotein 32
Ppp1r1b protein, mouse
Ppp1r1b protein, rat
adducin
Caffeine
Cocaine

Abstract

Publication types

MeSH terms

Substances

Grants and funding