Glutamate receptor subunit 2 Serine 880 phosphorylation modulates synaptic transmission and mediates plasticity in CA1 pyramidal cells.
The cytoplasmic C termini of AMPA receptor subunits contain PDZ (postsynaptic density 95/Discs large/zona occludens 1) ligand domains that can control their synaptic trafficking during plasticity. The glutamate receptor subunit 2 (GluR2) PDZ ligand domain can be phosphorylated at serine 880 (S880), and this disrupts interactions with GRIP/ABP (glutamate receptor-interacting protein/AMPA-binding protein) but not with PICK1 (PKC-interacting protein 1). Here, the impact of GluR2 S880 phosphorylation on synaptic transmission and plasticity was explored by expressing, in hippocampal slice cultures, GluR2 subunits containing point mutations that mimic or prevent phosphorylation at this residue. Our results indicate that mimicking GluR2 S880 phosphorylation excludes these receptors from synapses, depresses transmission, and partially occludes long-term depression (LTD). Conversely, mutations that prevent phosphorylation reduce LTD. Disruption of the interaction between GluR2 and GRIP/ABP by S880 phosphorylation may thus facilitate removal of synaptic AMPA receptors and mediate some forms of activity-dependent synaptic depression.
Seidenman
Kenneth J
KJ
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Steinberg
Jordan P
JP
Huganir
Richard
R
Malinow
Roberto
R
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D036881:Long-Term Synaptic Depression / Q000502:physiology; D018716:Molecular Mimicry / Q000235:genetics / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C491309:Grip1 protein, mouse; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D021122:Protein Subunits; D018091:Receptors, AMPA; D012694:Serine; C104722:glutamate receptor ionotropic, AMPA 2