RGD Reference Report - REST-dependent epigenetic remodeling promotes the developmental switch in synaptic NMDA receptors. - Rat Genome Database

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REST-dependent epigenetic remodeling promotes the developmental switch in synaptic NMDA receptors.

Authors: Rodenas-Ruano, Alma  Chávez, Andrés E  Cossio, Maria J  Castillo, Pablo E  Zukin, R Suzanne 
Citation: Rodenas-Ruano A, etal., Nat Neurosci. 2012 Oct;15(10):1382-90. doi: 10.1038/nn.3214. Epub 2012 Sep 9.
RGD ID: 14397585
Pubmed: PMID:22960932   (View Abstract at PubMed)
PMCID: PMC3501125   (View Article at PubMed Central)
DOI: DOI:10.1038/nn.3214   (Journal Full-text)

NMDA receptors (NMDARs) are critical to synaptogenesis, neural circuitry and higher cognitive functions. A hallmark feature of NMDARs is an early postnatal developmental switch from those containing primarily GluN2B to primarily GluN2A subunits. Although the switch in phenotype has been an area of intense interest for two decades, the mechanisms that trigger it and the link between experience and the switch are unclear. Here we show a new role for the transcriptional repressor REST in the developmental switch of synaptic NMDARs. REST is activated at a critical window of time and acts via epigenetic remodeling to repress Grin2b expression and alter NMDAR properties at rat hippocampal synapses. Knockdown of REST in vivo prevented the decline in GluN2B and developmental switch in NMDARs. Maternal deprivation impaired REST activation and acquisition of the mature NMDAR phenotype. Thus, REST is essential for experience-dependent fine-tuning of genes involved in synaptic plasticity.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RestRatmodification of synaptic structure involved_inIMP PMID:22960932UniProt 
RestRatnegative regulation of transcription by RNA polymerase II involved_inIMP PMID:22960932UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Rest  (RE1-silencing transcription factor)


Additional Information