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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

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

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. More... »

PAGES

10099

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms10099

    DOI

    http://dx.doi.org/10.1038/ncomms10099

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1004945690

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26639316


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