| 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 postsynapse organization (GO:0099175) |
| 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.2, 5, 8 |
| Annotation description: | Fig.2: "Epac2 activation induces dendritic spine shrinkage, reduces presynaptic contact and enhances spine motility and turnover" - "To determine the requirement for Epac2 for basal and 8-CPT-induced spine morphology, we knocked down endogenous Epac2. Neurons were transfected with Epac2-specific shRNA that coexpressed GFP; in RNAi-expressing neurons, 8-CPT was incapable of inducing spine shrinkage, demonstrating that normal levels of Epac2 expression were required for 8-CPT-dependent spine shrinkage (Fig. 2a-b). Epac2 knockdown caused increased basal average spine area. This effect was rescued by overexpression of a "rescue Epac2" mutant, in which 3 silent point mutations have been introduced to render it RNAi-insensitive, demonstrating the specificity of the knockdown (Fig. 2a-b). RNAi knockdown of Epac2 did not affect spine density (Supplementary Fig. 6d-e)." Fig.5: "Dopamine D1/D5-like receptors modulate Rap activity, spine morphology, and GluR2 surface expression" - "In the presence of Epac2 RNAi, the effect of SKF-38393 on dendritic spines was occluded (Fig. 5c-d); treatment with SKF-38393 did not affect linear density (Supplementary Fig. 6e). Furthermore, SKF-38393 caused a significant reduction in surface GluR2 on spines (Fig. 5c, e) (*P<0.001). This effect required Epac2, as it did not occur when Epac2 was knocked down." Fig.8: "Epac2 missense mutants affect spine morphology" |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA |
| Evidence tracking, Experiment Assay: | Confocal |
| 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: | 2851 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |