Early Growth Response 1 (Egr-1) Regulates N-Methyl-d-aspartate Receptor (NMDAR)-dependent Transcription of PSD-95 and α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor (AMPAR) Trafficking in Hippocampal Primary Neurons.

TitleEarly Growth Response 1 (Egr-1) Regulates N-Methyl-d-aspartate Receptor (NMDAR)-dependent Transcription of PSD-95 and α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor (AMPAR) Trafficking in Hippocampal Primary Neurons.
Publication TypeJournal Article
Year of Publication2015
AuthorsQin X, Jiang Y, Tse YChung, Wang Y, Wong TPan, Paudel HK
JournalJ Biol Chem
Volume290
Issue49
Pagination29603-16
Date Published2015 Dec 04
ISSN1083-351X
KeywordsAnimals, Cercopithecus aethiops, COS Cells, Early Growth Response Protein 1, Electrophysiology, Endocytosis, Guanylate Kinases, Hippocampus, Humans, Long-Term Synaptic Depression, Membrane Proteins, Memory, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Confocal, Neuronal Plasticity, Neurons, Promoter Regions, Genetic, Rats, Receptors, AMPA, Receptors, N-Methyl-D-Aspartate, Signal Transduction
Abstract

The N-methyl-d-aspartate receptor (NMDAR) controls synaptic plasticity and memory function and is one of the major inducers of transcription factor Egr-1 in the hippocampus. However, how Egr-1 mediates the NMDAR signal in neurons has remained unclear. Here, we show that the hippocampus of mice lacking Egr-1 displays electrophysiology properties and ultrastructure that are similar to mice overexpressing PSD-95, a major scaffolding protein of postsynaptic density involved in synapse formation, synaptic plasticity, and synaptic targeting of AMPA receptors (AMPARs), which mediate the vast majority of excitatory transmission in the CNS. We demonstrate that Egr-1 is a transcription repressor of the PSD-95 gene and is recruited to the PSD-95 promoter in response to NMDAR activation. Knockdown of Egr-1 in rat hippocampal primary neurons blocks NMDAR-induced PSD-95 down-regulation and AMPAR endocytosis. Likewise, overexpression of Egr-1 in rat hippocampal primary neurons causes reduction in PSD-95 protein level and promotes AMPAR endocytosis. Our data indicate that Egr-1 is involved in NMDAR-mediated PSD-95 down-regulation and AMPAR endocytosis, a process important in the expression of long term depression.

DOI10.1074/jbc.M115.668889
Alternate JournalJ. Biol. Chem.
PubMed ID26475861
PubMed Central IDPMC4705959
Grant List / / Canadian Institutes of Health Research / Canada

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