The NMDA receptor subunit GluN3A regulates synaptic activity-induced and myocyte enhancer factor 2C (MEF2C)-dependent transcription.
Journal Article (Journal Article)
N-Methyl-d-aspartate type glutamate receptors (NMDARs) are key mediators of synaptic activity-regulated gene transcription in neurons, both during development and in the adult brain. Developmental differences in the glutamate receptor ionotropic NMDA 2 (GluN2) subunit composition of NMDARs determines whether they activate the transcription factor cAMP-responsive element-binding protein 1 (CREB). However, whether the developmentally regulated GluN3A subunit also modulates NMDAR-induced transcription is unknown. Here, using an array of techniques, including quantitative real-time PCR, immunostaining, reporter gene assays, RNA-Seq, and two-photon glutamate uncaging with calcium imaging, we show that knocking down GluN3A in rat hippocampal neurons promotes the inducible transcription of a subset of NMDAR-sensitive genes. We found that this enhancement is mediated by the accumulation of phosphorylated p38 mitogen-activated protein kinase in the nucleus, which drives the activation of the transcription factor myocyte enhancer factor 2C (MEF2C) and promotes the transcription of a subset of synaptic activity-induced genes, including brain-derived neurotrophic factor (Bdnf) and activity-regulated cytoskeleton-associated protein (Arc). Our evidence that GluN3A regulates MEF2C-dependent transcription reveals a novel mechanism by which NMDAR subunit composition confers specificity to the program of synaptic activity-regulated gene transcription in developing neurons.
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Duke Authors
Cited Authors
- Chen, L-F; Lyons, MR; Liu, F; Green, MV; Hedrick, NG; Williams, AB; Narayanan, A; Yasuda, R; West, AE
Published Date
- June 19, 2020
Published In
Volume / Issue
- 295 / 25
Start / End Page
- 8613 - 8627
PubMed ID
- 32393578
Pubmed Central ID
- PMC7307204
Electronic International Standard Serial Number (EISSN)
- 1083-351X
Digital Object Identifier (DOI)
- 10.1074/jbc.RA119.010266
Language
- eng
Conference Location
- United States