Abstract
Cerebellar LTD requires activation of PKC and is expressed, at least in part, as postsynaptic AMPA receptor internalization. Recently, it was shown that AMPA receptor internalization requires clathrin-mediated endocytosis and depends upon the carboxy-terminal region of GluR2/3. Phosphorylation of Ser-880 in this region by PKC differentially regulates the binding of the PDZ domain-containing proteins GRIP/ABP and PICK1. Peptides, corresponding to the phosphorylated and dephosphorylated GluR2 carboxy-terminal PDZ binding motif, were perfused in cerebellar Purkinje cells grown in culture. Both the dephospho form (which blocks binding of GRIP/ABP and PICK1) and the phospho form (which selectively blocks PICK1) attenuated LTD induction by glutamate/depolarization pairing, as did antibodies directed against the PDZ domain of PICK1. These findings indicate that expression of cerebellar LTD requires PKC-regulated interactions between the carboxy-terminal of GluR2/3 and PDZ domain-containing proteins.
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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Adaptor Proteins, Signal Transducing
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Amino Acid Motifs / immunology
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Amino Acid Motifs / physiology
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Animals
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Antibodies / pharmacology
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Binding, Competitive / drug effects
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Calcium / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Carrier Proteins / metabolism
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Cell Cycle Proteins
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Cells, Cultured
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Cerebellum / cytology
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Cerebellum / metabolism*
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Mice
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Nerve Tissue Proteins / metabolism
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Neural Inhibition / drug effects
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Neural Inhibition / physiology*
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Neuronal Plasticity / drug effects
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Nuclear Proteins / genetics
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Nuclear Proteins / immunology
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Nuclear Proteins / metabolism
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Patch-Clamp Techniques
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Phosphorylation
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Protein Kinase C / metabolism*
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Protein Structure, Tertiary / physiology
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Purkinje Cells / cytology
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Purkinje Cells / drug effects
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Purkinje Cells / metabolism
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Receptors, AMPA / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / pharmacology
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Time
Substances
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Adaptor Proteins, Signal Transducing
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Antibodies
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Carrier Proteins
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Cell Cycle Proteins
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Grip1 protein, mouse
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Nerve Tissue Proteins
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Nuclear Proteins
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Peptide Fragments
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Prkcabp protein, mouse
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Receptors, AMPA
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Recombinant Fusion Proteins
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glutamate receptor ionotropic, AMPA 3
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Protein Kinase C
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glutamate receptor ionotropic, AMPA 2
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Calcium