title: Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins.
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.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: J
authors.initials: J
authors.lastname: Xia
authors.forename: H J
authors.initials: HJ
authors.lastname: Chung
authors.forename: C
authors.initials: C
authors.lastname: Wihler
authors.forename: R L
authors.initials: RL
authors.lastname: Huganir
authors.forename: D J
authors.initials: DJ
authors.lastname: Linden
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs / Q000276:immunology / Q000502:physiology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D013995:Time
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C491309:Grip1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; C091822:Prkcabp protein, mouse; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; C104723:glutamate receptor ionotropic, AMPA 3; D011493:Protein Kinase C; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium