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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Calcium / metabolism
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Carrier Proteins / metabolism
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Cell Cycle Proteins
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Cells, Cultured
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Cerebellar Cortex / cytology
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Cerebellar Cortex / physiology*
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Enzyme Activation
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Excitatory Postsynaptic Potentials
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Intracellular Signaling Peptides and Proteins
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Long-Term Synaptic Depression*
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Mice
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Mice, Knockout
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Nerve Tissue Proteins / metabolism
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Nuclear Proteins / metabolism
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Nuclear Receptor Coactivator 2
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Patch-Clamp Techniques
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Phorbol Esters / pharmacology
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Phosphorylation
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Phosphoserine / metabolism
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Point Mutation
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Protein Binding
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Protein Kinase C / metabolism
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Purkinje Cells / physiology*
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism*
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Transcription Factors / metabolism
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Transfection
Substances
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Carrier Proteins
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Cell Cycle Proteins
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Grip2 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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Nuclear Receptor Coactivator 2
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Phorbol Esters
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Prkcabp protein, mouse
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Receptors, AMPA
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Transcription Factors
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Phosphoserine
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phorbol-12,13-diacetate
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Protein Kinase C
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glutamate receptor ionotropic, AMPA 2
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Calcium