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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Dopamine and cAMP-Regulated Phosphoprotein 32
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Electrophysiology
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Enzyme Inhibitors / metabolism*
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Ion Channels / metabolism*
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Ion Channels / physiology
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Microfilament Proteins / metabolism*
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Neostriatum / cytology
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Neostriatum / metabolism*
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Nerve Tissue Proteins / physiology*
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Neurons / metabolism
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Phosphoprotein Phosphatases / metabolism
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Phosphoprotein Phosphatases / physiology*
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Phosphoproteins*
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Protein Phosphatase 1
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Rats
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Receptors, AMPA / metabolism*
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Receptors, AMPA / physiology
Substances
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Dopamine and cAMP-Regulated Phosphoprotein 32
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Enzyme Inhibitors
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Ion Channels
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Microfilament Proteins
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Nerve Tissue Proteins
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Phosphoproteins
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Receptors, AMPA
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neurabin
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Phosphoprotein Phosphatases
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Protein Phosphatase 1