title: Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression.
abstract: Cerebellar long-term depression (LTD) is a model of synaptic memory that requires protein kinase C (PKC) activation and is expressed as a reduction in the number of postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. LTD was absent in cultured cerebellar Purkinje cells from mutant mice lacking the AMPA receptor GluR2 subunit and could be rescued by transient transfection with the wild-type GluR2 subunit. Transfection with a point mutant that eliminated PKC phosphorylation of Ser880 in the carboxy-terminal PDZ ligand of GluR2 failed to restore LTD. In contrast, transfection with a point mutant that mimicked phosphorylation at Ser880 occluded subsequent LTD. Thus, PKC phosphorylation of GluR2 Ser880 is a critical event in the induction of cerebellar LTD.
authors.affiliation: Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Chung
authors.forename: Jordan P
authors.initials: JP
authors.lastname: Steinberg
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: David J
authors.initials: DJ
authors.lastname: Linden
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000502:physiology*; D004789:Enzyme Activation; D019706:Excitatory Postsynaptic Potentials; D047908:Intracellular Signaling Peptides and Proteins; D036881:Long-Term Synaptic Depression; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D051958:Nuclear Receptor Coactivator 2; D018408:Patch-Clamp Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D011689:Purkinje Cells / Q000502:physiology*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C485567:Grip2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D010703:Phorbol Esters; C091822:Prkcabp protein, mouse; D018091:Receptors, AMPA; D014157:Transcription Factors; D010768:Phosphoserine; C008874:phorbol-12,13-diacetate; D011493:Protein Kinase C; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium