RGD Reference Report - Epac2 induces synapse remodeling and depression and its disease-associated forms alter spines. - Rat Genome Database

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Epac2 induces synapse remodeling and depression and its disease-associated forms alter spines.

Authors: Woolfrey, KM  Srivastava, DP  Photowala, H  Yamashita, M  Barbolina, MV  Cahill, ME  Xie, Z  Jones, KA  Quilliam, LA  Prakriya, M  Penzes, P 
Citation: Woolfrey KM, etal., Nat Neurosci. 2009 Oct;12(10):1275-84. Epub 2009 Sep 6.
RGD ID: 2314692
Pubmed: PMID:19734897   (View Abstract at PubMed)
PMCID: PMC2754861   (View Article at PubMed Central)
DOI: DOI:10.1038/nn.2386   (Journal Full-text)

Dynamic remodeling of spiny synapses is crucial for cortical circuit development, refinement and plasticity, whereas abnormal morphogenesis is associated with neuropsychiatric disorders. We found that activation of Epac2, a PKA-independent cAMP target and Rap guanine-nucleotide exchange factor (GEF), in cultured rat cortical neurons induced spine shrinkage, increased spine motility, removed synaptic GluR2/3-containing AMPA receptors and depressed excitatory transmission, whereas its inhibition promoted spine enlargement and stabilization. Epac2 was required for dopamine D1-like receptor-dependent spine shrinkage and GluR2 removal from spines. Epac2 interaction with neuroligin promoted its membrane recruitment and enhanced its GEF activity. Rare missense mutations in the EPAC2 (also known as RAPGEF4) gene, previously found in individuals with autism, affected basal and neuroligin-stimulated GEF activity, dendritic Rap signaling, synaptic protein distribution and spine morphology. Thus, we identify a previously unknown mechanism that promotes dynamic remodeling and depression of spiny synapses, disruption of which may contribute to some aspects of disease.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rapgef4Rataxon  IDA  RGD 
Rapgef4Ratdendrite  IDA  RGD 
Rapgef4Ratdendritic spine  IDA  RGD 
Rapgef4Ratexcitatory synapse  IDA  RGD 
Rapgef4Ratglutamatergic synapse is_active_inEXP PMID:19734897SynGO 
Rapgef4Ratglutamatergic synapse is_active_inIDA PMID:19734897SynGO 
Rapgef4Ratglutamatergic synapse is_active_inIMP PMID:19734897SynGO 
Rapgef4Ratpostsynaptic density is_active_inIDA PMID:19734897SynGO 
Rapgef4Ratpresynapse is_active_inEXP PMID:19734897SynGO 
Rapgef4Ratpresynapse is_active_inIDA PMID:19734897SynGO 
Rapgef4Ratprotein-containing complex  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rapgef4Ratprotein binding  IPINlgn1 (Rattus norvegicus) more ... RGD 
Rapgef4Ratprotein-containing complex binding  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rapgef4  (Rap guanine nucleotide exchange factor 4)


Additional Information