| Annotated protein: | Neurofibromin (Neurofibromatosis-related protein NF-1). Gene symbol: NF1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q04690 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ NF1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynapse organization (GO:0099175) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Wang HF, et al. "Valosin-containing protein and neurofibromin interact to regulate dendritic spine density" J Clin Invest. 2011 Dec;121(12):4820-37 PMID:22105171 |
| Figure(s): | fig 1, S1, 5b-f & 6 |
| Annotation description: | From Results section: "Compared with WT littermates, the spine densities of CA1 pyramidal neurons in Nf1+/- mice were significantly lower, irrespective of whether first-, second-, or higher-order branches of apical dendrites were analyzed (Figure 1). These results support a role for the Nf1 gene in the regulation of dendritic spine density in mouse brain." "a neurofibromin antibody was employed to identify the neurofibromin-associated proteins by co-immunoprecipitation from rat brain extracts" (...) "the most robust protein precipitated by neurofibromin antibody (...) was identified as VCP using both MALDI-TOF (Supplemental Figure 1B) and MS/MS analyses (Supplemental Figure 1C)." (...) "In addition to VCP, p47, a cofactor of VCP, was also present in the precipitate of neurofibromin antibodies (Supplemental Figure 1, A and B), suggesting that neurofibromin forms a complex with VCP and p47." (...) VCP was coprecipitated by neurofibromin antibody (Figure 2A). The reciprocal immunoprecipitation also showed the precipitation of neurofibromin by VCP antibody from rat brain extracts (Figure 2A)." (...) "The presence of p47 in the neurofibromin protein complex was also confirmed by co-immunoprecipitation." "the LRD fragment (Figure 5A), a region of neurofibromin interacting with VCP, was overexpressed in cultured hippocampal neurons. Compared with vector control, expression of the LRD fragment reduced the spine density of cultured hippocampal neurons (Figure 5, B-D; KS test in Figure 5C, control vs. WT LRD, P < 0.001; t test in Figure 5D, control vs. LRD, P < 0.001), supporting the role of the interaction between neurofibromin and VCP in the regulation of dendritic spine density." "When compared with WT LRD, T1787M, C1909R, and A1655T mutations did not noticeably affect the interaction between the LRD domain and the D1D2 region or fulllength VCP (Figure 5, E and F). By contrast, deletion of the residue Y1587 almost completely abolished this interaction (Figure 5, E and F)." "expression of the LRD Y1587Δ mutant did not reduce spine number (Figure 5, B-D; KS test in Figure 5C, control vs. Y1587Δ, P = 0.83; WT LRD vs. Y1587Δ, P < 0.001; t test in Figure 5D, control vs. Y1587Δ, P = 0.85; WT LRD vs. Y1587Δ, P < 0.001). By contrast, the LRD C1909R mutant, which is capable of interacting with VCP, was able to reduce the spine density (Figure 5, B-D; KS test in Figure 5C, control vs. C1909R, P = 0.002; t test in Figure 5D, control vs. C1909R, P < 0.001), though the inhibitory effect was significantly weaker than that of WT LRD (Figure 5, B-D; KS test in Figure 5C, P < 0.001; t test in Figure 5D, P < 0.001). In conclusion, the results of these analyses suggest that the Y1587Δ mutation in the NF1 gene disrupts the interaction between neurofibromin and VCP and, as a result, affects dendritic spinogenesis." "compared with vector control, expression of full-length rNf1 increased the density of dendritic protrusion in Nf1+/- cortical neurons at 10 DIV (Figure 6, A-C; Nf1+/- control vs. Nf1+/- rNf1, t test, P < 0.001; KS test, P = 0.007) as well as at 18 DIV (Figure 6, D-F; Nf1+/- control vs. Nf1+/- rNf1, t test, P < 0.001; KS test, P < 0.001). By contrast, expression of the full-length Y1587Δ mutant did not increase the protrusion density in Nf1+/- neurons at 10 DIV (Figure 6, A-C; Nf1+/- rNf1 vs. Nf1+/- Y1587Δ, t test, P < 0.001; KS test, P < 0.001) or at 18 DIV (Figure 6, D-F; Nf1+/- rNf1 vs. Nf1+/- Y1587Δ, t test, P < 0.001; KS test, P < 0.001). These results support the importance of the residue Y1587 for the activity of neurofibromin in controlling spine density." |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Over-expression Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal |
| Annotator(s): | Rita Reig-Viader (ORCID:0000-0002-6893-6177) Àlex Bayés (ORCID:0000-0002-5265-6306) |
| Lab: | Molecular Physiology of the Synapse Laboratory, Biomedical Research Institute Sant Pau, 08025 Barcelona, Spain and and Universitat Autnoma de Cerdanyola del Valls, Spain Barcelona, 08193 Bellaterra |
| SynGO annotation ID: | 3081 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |