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.
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We thank Takuo Watanabe for providing [32P]phosphorylase a. This work was supported by a National Parkinson Foundation grant (Z.Y.) and U.S. Public Health Service Grants MH 40899 and DA 10044 (P.G.).
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Yan, Z., Hsieh–Wilson, L., Feng, J. et al. Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP–32 and spinophilin. Nat Neurosci 2, 13–17 (1999). https://doi.org/10.1038/4516
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