Annotated protein: | Neurofibromin (Neurofibromatosis-related protein NF-1). Gene symbol: NF1. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: P97526 |
antibody wiki: | |
SynGO gene info: | SynGO data @ NF1 |
Ontology domain: | Biological Process |
SynGO term: | postsynaptic signaling pathway (GO:0098926) |
Synapse type(s): | hippocampus, glutamatergic |
Annotated paper: | Oliveira AF, et al. "Neurofibromin is the major ras inactivator in dendritic spines" J Neurosci. 2014 Jan 15;34(3):776-83 PMID:24431436 |
Figure(s): | fig 1b-e; 3a-f, 3i-k; 4 & 5 |
Annotation description: | From Results section: "In control neurons expressing scrambled shRNA (sc-shRNA), the stimulated dendritic spine displayed a rapid increase in volume within 1 min after the stimulation (transient phase; Fig. 1B-D), and then the spine volume decayed over 5 min to a smaller sustained enlargement that was maintained for >30min (sustained phase; Fig. 1B,C,E)." (...) "In contrast, in neurons transfected with sh-NF1s, spine structural plasticity was significantly impaired during both transient and sustained phases (Fig. 1B-E). Overexpression of the GAP-related domain of neurofibromin (NF1-GRD; RasGAP domain) by itself did not cause any effects on structural plasticity, but rescued structural plasticity when coexpressed with sh-NF1 (Fig. 1B-E). These data suggest that Ras inactivation by neurofibromin is required for normal spine structural plasticity." "It has been reported that high Mg2+ inhibits circuit activity in organotypic slice cultures (Zhu et al., 2000) and significantly reduces Ras activation evoked by spontaneous neuronal activity (Zhu et al., 2002; Harvey et al., 2008). Under this condition, the impairment of spine enlargement by neurofibromin knock-down was rescued, indicating that the phenotype is due to spontaneous neuronal activity (Fig. 1B-E). These results suggest that the impaired spine plasticity in neurons expressing sh-NF1 is due to reduced inactivation of Ras evoked by spontaneous neuronal activity" "wedownregulated neurofibromin with sh-NF1 and imaged Ras activity with a FRET/FLIM Ras activation sensor, FRas2-M" (...) "we inhibited spontaneous network activity during expression of the sensor and shRNA with high Mg2+" (...) "sh-NF1 did not impair spine structural plasticity in neurons expressing the Ras sensor under this condition (Figs. 1, 3I-K)." "In control neurons, when 2-photon glutamate uncaging was applied near a single spine, Ras activity was rapidly increased within 1 min in the stimulated spine and decayed over 10 min (Fig. 3A,B,D)." (...) "In neurons expressing sh-NF1, the basal Ras activity in dendritic spines was higher (Fig. 3C), and, after glutamate uncaging, Ras was activated to a similar level to the control condition. However, Ras activation decayed much more slowly (Fig. 3D). Curve-fitting analyses indicate that the rate of Ras inactivation in neurons expressing sh-NF1 was only 10% of that in control neurons, whereas the peak amplitude of Ras activation did not show significant change (Fig. 3D-F). In contrast, in neurons expressing NF1-GRD, the basal activity was lower (Fig. 3C) and, after single spine stimulation, Ras activity decayed faster than in control neurons (Fig. 3D,F). These data indicate that neurofibromin is the major Ras inactivator in dendritic spines and is required for rapid inactivation of Ras." "Neurons expressing sh-NF1 showed reduced spine density after 5-7 d of transfection and the phenotype was rescued by overexpressing NF1-GRD or a dominant-negative Ras (Fig. 4A,B). In addition, inhibition of NMDARs with AP5 (100 uM) or neuronal activity with MgCl2 (10 mM) in the medium during the culture restored normal spine density (Fig. 4D-G). We observed no effects of sh-NF1 expression on the relative volume of dendritic spines, measured as fluorescence intensity within the spine normalized to that in the thick primary dendrite (Fig. 4C). These results suggest that hyperactivation of the NMDAR-Ras pathway due to knock-down of neurofibromin results in spine loss." "we observed reduced frequency of mEPSCs in neurons expressing sh-NF1 compared with untransfected neurons or with neurons expressing scshRNA (Fig. 5A,B). Conversely, the amplitude of mEPSCs was similar between control neurons and those expressing sh-NF1 (Fig. 5A,C). Therefore, these results suggest that neurofibromin plays an important role in the maintenance of spine structure by inactivating Ras rapidly." |
Evidence tracking, Biological System: | Intact tissue |
Evidence tracking, Protein Targeting: | Over-expression Antagonist / agonist |
Evidence tracking, Experiment Assay: | Two-photon microscopy Whole-cell patch clamp FRET |
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: | 3080 |
Dataset release (version): | 20231201 |
View annotation as GO-CAM model: |