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Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by DARPP–32 and spinophilin

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.

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Figure 1: Regulation of AMPA currents by a D1–class dopamine receptor agonist and by a protein phosphatase inhibitor.
Figure 2: Regulation of AMPA currents and PP–1 activity by DARPP–32.
Figure 3: Regulation of AMPA currents and of PP–1 anchoring by the spinophilin peptide.

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Acknowledgements

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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Correspondence to Paul Greengard.

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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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