PDZ proteins interacting with C-terminal GluR2/3 are involved in a PKC-dependent regulation of AMPA receptors at hippocampal synapses.
We investigated the role of PDZ proteins (GRIP, ABP, and PICK1) interacting with the C-terminal GluR2 by infusing a ct-GluR2 peptide ("pep2-SVKI") into CA1 pyramidal neurons in hippocampal slices using whole-cell recordings. Pep2-SVKI, but not a control or PICK1 selective peptide, caused AMPAR-mediated EPSC amplitude to increase in approximately one-third of control neurons and in most neurons following the prior induction of LTD. Pep2-SVKI also blocked LTD; however, this occurred in all neurons. A PKC inhibitor prevented these effects of pep2-SVKI on synaptic transmission and LTD. We propose a model in which the maintenance of LTD involves the binding of AMPARs to PDZ proteins to prevent their reinsertion. We also present evidence that PKC regulates AMPAR reinsertion during dedepression.
Daw
M I
MI
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, University Walk, BS8 1TD, Bristol, United Kingdom.
Chittajallu
R
R
Bortolotto
Z A
ZA
Dev
K K
KK
Duprat
F
F
Henley
J M
JM
Collingridge
G L
GL
Isaac
J T
JT
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; C491309:Grip1 protein, mouse; C491308:Grip1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D010446:Peptide Fragments; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; C104723:glutamate receptor ionotropic, AMPA 3; C577293:pep2-SVKI; D011493:Protein Kinase C; C104722:glutamate receptor ionotropic, AMPA 2