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 and Jean-Antoine Girault ()
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Olivia Engmann: Inserm UMR-S 839
Albert Giralt: Inserm UMR-S 839
Nicolas Gervasi: Inserm UMR-S 839
Lucile Marion-Poll: Inserm UMR-S 839
Laila Gasmi: Inserm UMR-S 839
Odile Filhol: Inserm, U1036, CEA
Marina R. Picciotto: Yale University School of Medicine
Diana Gilligan: Upstate University Hospital, SUNY Upstate University
Paul Greengard: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University
Angus C. Nairn: Yale University School of Medicine
Denis Hervé: Inserm UMR-S 839
Jean-Antoine Girault: Inserm UMR-S 839

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms10099

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