Abstract
Dynamic regulation of ion channel interactions with the cytoskeleton mediates aspects of synaptic plasticity, yet mechanisms for this process are largely unknown. Here, we report that two inwardly rectifying K+ channels, Kir 2.1 and 2.3, bind to PSD-95, a cytoskeletal protein of postsynaptic densities that clusters NMDA receptors and voltage-dependent K+ channels. Kir 2.3 colocalizes with PSD-95 in neuronal populations in forebrain, and a PSD-95/Kir 2.3 complex occurs in hippocampus. Within the C-terminal tail of Kir 2.3, a serine residue critical for interaction with PSD-95, is also a substrate for phosphorylation by protein kinase A (PKA). Stimulation of PKA in intact cells causes rapid dissociation of the channel from PSD-95. This work identifies a physiological mechanism for regulating ion channel interactions with the postsynaptic density.
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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Amino Acid Sequence
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Animals
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Binding Sites
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Blotting, Western
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Calcimycin / pharmacology
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Cell Line
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Colforsin / pharmacology
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Humans
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Kidney
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Mammals
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Molecular Sequence Data
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Nerve Tissue Proteins / metabolism*
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Peptide Fragments / chemistry
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Peptide Fragments / immunology
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Phosphorylation
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Potassium Channels / chemistry
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Potassium Channels / metabolism*
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Potassium Channels, Inwardly Rectifying*
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Proto-Oncogene Proteins c-myc / chemistry
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Proto-Oncogene Proteins c-myc / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Homology, Amino Acid
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Tetradecanoylphorbol Acetate / pharmacology
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Transfection
Substances
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KCNJ4 protein, human
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Nerve Tissue Proteins
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Peptide Fragments
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Potassium Channels
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Potassium Channels, Inwardly Rectifying
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Proto-Oncogene Proteins c-myc
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Recombinant Proteins
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postsynaptic density proteins
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Colforsin
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Calcimycin
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Cyclic AMP-Dependent Protein Kinases
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Tetradecanoylphorbol Acetate