Protein phosphatase 1 modulation of neostriatal AMPA channels: Regulation by DARPP-32 and spinophilin

Zhen Yan, Linda Hsieh-Wilson, Jian Feng, Kazuhito Tomizawa, Patrick B. Allen, Allen A. Fienberg, Angus C. Nairn, Paul Greengard

    Research output: Contribution to journalArticlepeer-review

    243 Citations (Scopus)

    Abstract

    Modulation of AMPA-type glutamate channels is important for synaptic plasticity. Here we provide physiological evidence that the activity of AMPA channels is regulated by protein phosphatase 1 (PP-1) in neostriatal neurons and identify two distinct molecular mechanisms of this regulation. One mechanism involves control of PP-1 catalytic activity by DARPP-32, a dopamine- and cAMP-regulated phosphoprotein highly enriched in neostriatum. The other involves binding of PP-1 to spinophilin, a protein that colocalizes PP-1 with AMPA receptors in postsynaptic densities. The results suggest that regulation of anchored PP-1 is important for AMPA-receptor-mediated synaptic transmission and plasticity.

    Original languageEnglish
    Pages (from-to)13-17
    Number of pages5
    JournalNature Neuroscience
    Volume2
    Issue number1
    DOIs
    Publication statusPublished - Jan 1999

    ASJC Scopus subject areas

    • Neuroscience(all)

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