| Annotated protein: | NEDD8-activating enzyme E1 regulatory subunit (Amyloid beta precursor protein-binding protein 1, 59 kDa) (APP-BP1) (Amyloid protein-binding protein 1). Gene symbol: NAE1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q8VBW6 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ NAE1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynapse assembly (GO:0150052) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Vogl AM, et al. "Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition" Nat Neurosci. 2015 Feb;18(2):239-51 PMID:25581363 |
| Figure(s): | Figure 8 |
| Annotation description: | Similar to ubiquitylation, neddylation requires three sequential reaction steps accomplished by the heterodimeric E1-activating enzyme NAE (Nedd8 activating enzyme), the conjugating enzyme Ubc12 and an as yet incompletely characterized set of E3 ligases (PMID:18793140). Figure 2,3: knockdown of Nedd8 and Ubc12, or using NAE inhibitor MLN-4924 (Fig. S2c & PMID:19360080), reduced dendritic spine maturation. Figure 4: Neddylation is active in synapses, as demonstrated by live imaging experiments that quantified the rates of de novo growth and elimination of spines in mature cultured neurons (DIV19) treated for 8 h with vehicle or MLN-4924. Figure 6, 7: molecular characterization of PSD95 (DLG4) neddylation further confirms this process takes place at the postsynapse. Figure 8, S9f: "To avoid the effects of neddylation on developmental stages, we generated Nae1-floxed mice and crossed them with CamKIIα-CreERT2 mice to generate the Nae1-CamKIIα-CreERT2 mouse line (Fig. S9a,b). ... Three to four weeks after tamoxifen administration, Nae1-CamKIIα-CreERT2 mice displayed a severe reduction in spine density and size in both cortical and hippocampal pyramidal neurons (Fig. 8a). The morphological changes were limited to spines, and the general neuron morphology remained unaffected." |
| Evidence tracking, Biological System: | Cultured neurons Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Confocal |
| Annotator(s): | Frank Koopmans (ORCID:0000-0002-4973-5732) 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: | 5258 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |