| Annotated protein: | Rap guanine nucleotide exchange factor 4 (Exchange factor directly activated by cAMP 2) (Exchange protein directly activated by cAMP 2) (EPAC 2) (cAMP-regulated guanine nucleotide exchange factor II) (cAMP-GEFII). Gene symbol: RAPGEF4. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q9Z1C7 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ RAPGEF4 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696) |
| Synapse type(s): | cerebral cortex, glutamatergic |
| Annotated paper: | Woolfrey KM, et al. "Epac2 induces synapse remodeling and depression and its disease-associated forms alter spines" Nat Neurosci. 2009 Oct;12(10):1275-84 PMID:19734897 |
| Figure(s): | Fig.3, 4 |
| Annotation description: | Fig.3: "Epac2 interacts with GluR2/3-containing AMPAR and removes them from spines" - "Following 8-CPT treatment, GluR2/3 content became significantly reduced in spines (Fig. 3b), and increased in shaft clusters. These effects were specifically dependent on Epac2; RNAi-mediated knockdown prevented 8-CPT-induced GluR2/3 removal from spines (Fig. 3c) (*P<0.01). RNAi expression did not alter GluR2/3 spine content, suggesting that Epac2 activation is only involved in GluR2/3 removal from synapses" Fig.4: "Epac2 activation depresses AMPAR-mediated synaptic transmission" - "To determine the functional outcome of this reduction in GluR2/3 content in spines, we examined the effects of 8-CPT on AMPAR-dependent miniature excitatory postsynaptic currents (mEPSCs) (Fig. 4). Incubation of neurons with 8-CPT (50 uM, 1 hr) resulted in a robust reduction of mean amplitudes (34%) and frequencies (59%) of AMPAR-mediated mEPSCs (Fig. 4a) (*P<0.05), resulting in a shift in the distribution of mEPSC amplitudes toward smaller values. RNAi-knockdown of Epac2 in postsynaptic neurons prevented 8-CPT-mediated reduction in basal mean mEPSC amplitude (Fig. 4a)" |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp IP + WB/MSMS |
| Annotator(s): | Pim van Nierop (ORCID:0000-0003-0593-3443) Guus Smit (ORCID:0000-0002-2286-1587) Matthijs Verhage (ORCID:0000-0002-2514-0216) |
| Lab: | Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands |
| SynGO annotation ID: | 2850 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |