Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression.
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.
Chung
Hee Jung
HJ
Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 USA.
Steinberg
Jordan P
JP
Huganir
Richard L
RL
Linden
David J
DJ
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
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