The NMDA receptor subunit GluN3A regulates synaptic activity-induced and myocyte enhancer factor 2C (MEF2C)-dependent transcription.
| dc.contributor.author | Chen, Liang-Fu | |
| dc.contributor.author | Lyons, Michelle R | |
| dc.contributor.author | Liu, Fang | |
| dc.contributor.author | Green, Matthew V | |
| dc.contributor.author | Hedrick, Nathan G | |
| dc.contributor.author | Williams, Ashley B | |
| dc.contributor.author | Narayanan, Arthy | |
| dc.contributor.author | Yasuda, Ryohei | |
| dc.contributor.author | West, Anne E | |
| dc.date.accessioned | 2020-06-01T15:36:13Z | |
| dc.date.available | 2020-06-01T15:36:13Z | |
| dc.date.issued | 2020-05-11 | |
| dc.date.updated | 2020-06-01T15:36:08Z | |
| dc.description.abstract | 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 sequencing, 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 (MAP) 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. | |
| dc.identifier | RA119.010266 | |
| dc.identifier.issn | 0021-9258 | |
| dc.identifier.issn | 1083-351X | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | American Society for Biochemistry & Molecular Biology (ASBMB) | |
| dc.relation.ispartof | The Journal of biological chemistry | |
| dc.relation.isversionof | 10.1074/jbc.ra119.010266 | |
| dc.subject | MEF2 transcription factors | |
| dc.subject | N-methyl-D-aspartate receptor (NMDA receptor, NMDAR) | |
| dc.subject | brain-derived neurotrophic factor (BDNF) | |
| dc.subject | excitation-transcription coupling | |
| dc.subject | gene regulation | |
| dc.subject | ionotropic glutamate receptor | |
| dc.subject | neurodevelopment | |
| dc.subject | p38 MAPK | |
| dc.subject | synaptic plasticity | |
| dc.title | The NMDA receptor subunit GluN3A regulates synaptic activity-induced and myocyte enhancer factor 2C (MEF2C)-dependent transcription. | |
| dc.type | Journal article | |
| duke.contributor.orcid | West, Anne E|0000-0003-0846-139X | |
| pubs.begin-page | jbc.RA119.010266 | |
| pubs.end-page | jbc.RA119.010266 | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Neurobiology | |
| pubs.organisational-group | Duke Institute for Brain Sciences | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | University Institutes and Centers | |
| pubs.organisational-group | Institutes and Provost's Academic Units | |
| pubs.publication-status | Published |