Phosphorylation of serine-880 in GluR2 by protein kinase C prevents its C terminus from binding with glutamate receptor-interacting protein.
Phosphorylation of the glutamate receptor is an important mechanism of synaptic plasticity. Here, we show that the C terminus of GluR2 of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor is phosphorylated by protein kinase C and that serine-880 is the major phosphorylation site. This phosphorylation also occurs in human embryonic kidney (HEK) cells by addition of 12-O-tetradecanoylphorbol 13-acetate. Our immunoprecipitation experiment revealed that the phosphorylation of serine-880 in GluR2 drastically reduced the affinity for glutamate receptor-interacting protein (GRIP), a synaptic PDZ domain-containing protein, in vitro and in HEK cells. This result suggests that modulation of serine-880 phosphorylation in GluR2 controls the clustering of AMPA receptors at excitatory synapses and consequently contributes to synaptic plasticity.
Matsuda
S
S
Laboratory for Memory and Learning, RIKEN Brain Science Institute, Saitama, Japan.
Mikawa
S
S
Hirai
H
H
D000595:Amino Acid Sequence; D000906:Antibodies; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012694:Serine; D013569:Synapses / Q000502:physiology; D014162:Transfection
D000906:Antibodies; D002352:Carrier Proteins; C491310:GRIP1 protein, human; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D011994:Recombinant Proteins; C108822:metabotropic glutamate receptor 2; D010768:Phosphoserine; D012694:Serine; D011493:Protein Kinase C