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PMID: 11573007 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 20 ·2001-09-25 ·Pages 11725-30

Kim CH, Chung HJ, Lee HK, Huganir RL

Abstract

The interaction of PDZ domain-containing proteins with the C termini of alpha-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) receptors has been suggested to be important in the regulation of receptor targeting to excitatory synapses. Recent studies have shown that the rapid internalization of AMPA receptors at synapses may mediate, at least in part, the expression of long-term depression (LTD). We have previously shown that phosphorylation of Ser-880 on the AMPA receptor GluR2 subunit differentially regulated the interaction of GluR2 with the PDZ domain-containing proteins GRIP1 and PICK1. Here, we show that induction of LTD in hippocampal slices increases phosphorylation of Ser-880 within the GluR2 C-terminal PDZ ligand, suggesting that the modulation of GluR2 interaction with GRIP1 and PICK1 may regulate AMPA receptor internalization during LTD. Moreover, postsynaptic intracellular perfusion of GluR2 C-terminal peptides that disrupt GluR2 interaction with PICK1 inhibit the expression of hippocampal LTD. These results suggest that the interaction of GluR2 with PICK1 may play a regulatory role in the expression of LTD in the hippocampus.

MeSH Terms
2-Amino-5-phosphonovalerate/pharmacology Animals Carbazoles/pharmacology Dendrites/drug effects,physiology Enzyme Inhibitors/pharmacology Excitatory Postsynaptic Potentials/drug effects,physiology Hippocampus/drug effects,physiology In Vitro Techniques Indoles/pharmacology Long-Term Potentiation/drug effects,physiology Male Neuronal Plasticity/drug effects,physiology Okadaic Acid/pharmacology Phorbol Esters/pharmacology Phosphorylation Protein Kinase C/antagonists & inhibitors Protein Subunits Rats Rats, Sprague-Dawley Receptors, AMPA/drug effects,physiology Serine/metabolism
Chemicals
Carbazoles Enzyme Inhibitors Indoles Phorbol Esters Protein Subunits Receptors, AMPA glutamate receptor ionotropic, AMPA 3 Go 6976 Okadaic Acid Serine 2-Amino-5-phosphonovalerate Protein Kinase C glutamate receptor ionotropic, AMPA 2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kim C H
Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chung H J
Lee H K
Huganir R L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.211132798
Published
2001-09-25
Pages
11725-30
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC58797
Subset
IM
Grants
NINDS NIH HHS · R01 NS036715 · United States
NINDS NIH HHS · NS36715 · United States
External Links
PubMed source DOI: 10.1073/pnas.211132798 PMC Full Text View journal details
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