title: 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.
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.
authors.affiliation: From The Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, and.
authors.forename: Xike
authors.initials: X
authors.lastname: Qin
authors.affiliation: From The Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, and Department of Neurology and Neurosurgery.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Douglas Mental Health University Institute, and Department of Psychiatry, McGill University, Montréal, Quebec H4H 1R3, Canada.
authors.forename: Yiu Chung
authors.initials: YC
authors.lastname: Tse
authors.affiliation: From The Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, and.
authors.forename: Yunling
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Douglas Mental Health University Institute, and Department of Psychiatry, McGill University, Montréal, Quebec H4H 1R3, Canada.
authors.forename: Tak Pan
authors.initials: TP
authors.lastname: Wong
authors.affiliation: From The Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, and Department of Neurology and Neurosurgery, hemant.paudel@mcgill.ca.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Paudel
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D000076122:Disks Large Homolog 4 Protein; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D004594:Electrophysiology; D004705:Endocytosis; D051528:Guanylate Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D036881:Long-Term Synaptic Depression; D008565:Membrane Proteins / Q000378:metabolism*; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D008565:Membrane Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D051528:Guanylate Kinases
keywords: PSD95; early growth response protein 1 (EGR1); endocytosis; neurobiology; transcription regulation; α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA receptor, AMPAR)