| Annotated protein: | NEDD8 (Neddylin) (Neural precursor cell expressed developmentally down-regulated protein 8) (NEDD-8) (Ubiquitin-like protein Nedd8). Gene symbol: NEDD8. Taxonomy: Mus musculus (Mouse). Uniprot ID: P29595 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ NEDD8 |
| 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 2, 3, 4, 6, 7 |
| 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 1: Nedd8 is the most abundantly expressed ubiquitin-like protein in neurons and is broadly expressed in the mouse brain. Figure 2: Inhibition of neddylation blocks spine maturation. shRNA knockdown of Nedd8 in DIV12 mouse hippocampal neurons strongly decreased dendritic spine density and increased the number of dendritic filopodia. Figure 2,3: knockdown of Ubc12 and using NAE inhibitor MLN-4924 (Fig. S2c & PMID:19360080) also 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. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Antagonist / agonist |
| 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: | 5251 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |