Binding of the inward rectifier K+ channel Kir 2.3 to PSD-95 is regulated by protein kinase A phosphorylation.
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.
Cohen
N A
NA
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Brenman
J E
JE
Snyder
S H
SH
Bredt
D S
DS
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D008322:Mammals; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010766:Phosphorylation; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
C099489:KCNJ4 protein, human; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; C033652:postsynaptic density proteins; D005576:Colforsin; D000001:Calcimycin; D017868:Cyclic AMP-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate