| Annotated protein: | Neuropilin-2 (Vascular endothelial cell growth factor 165 receptor 2). Gene symbol: NRP2. Taxonomy: Mus musculus (Mouse). Uniprot ID: O35375 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ NRP2 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynapse organization (GO:0099175) |
| Synapse type(s): | cerebral cortex, glutamatergic |
| Annotated paper: | Tran TS, et al. "Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS" Nature. 2009 Dec 24;462(7276):1065-9 PMID:20010807 |
| Figure(s): | Fig. 2, Fig. 3, Sup Fig. 6, Sup Fig. 7, Sup Fig. 8 |
| Annotation description: | Fig. 2 and Sup. Fig. 6. in cortical neurons from NRP2 KO mice the frequency of mEPSCs is increased. Literal: "We performed whole-cell voltage clamp recordings to assess mEPSCs in layer V pyramidal neurons and DG GCs in acute brain slices derived from 3-4-week-old Npn-22/2 and wild-type mice (Fig. 2e and Supplementary Fig. 6). We observed a 2.4- and 1.5-fold increase in mEPSC frequency in Npn-22/2 layer V neurons and DG GCs, respectively, compared to wild-type littermates. Although we observed a slight decrease in the rise time and tau decay for layer V neurons, no significant change in amplitude was observed compared to wild-type littermates (Fig. 2e and Supplementary Fig. 6a). No significant difference in the paired-pulse amplitude ratio was observed between Npn-22/2 and wild-type neurons from layer V or DG (Supplementary Fig. 6), indicating that the increase in mEPSC frequency found in Npn-22/2 mutant mice is due to an increase in the number of synapses rather than an increase in the probability of presynaptic release. These results show that Sema3F-Npn-2 signalling negatively regulates both excitatory synapse number and synaptic transmission in layer V and DG neurons. Fig. 3, Sup Fig. 7, Sup Fig. 8 and Sup Fig. 9, NRP2 regulates spine morphology and synaptic ultrastructure in vivo Literal: "To determine how loss of Sema3F and Npn-2 influences synapse formation in vivo, we used transmission electron microscopy (TEM) to visualize dendritic spine ultrastructure and excitatory synapse morphology. Spines protruding from the dendritic shafts of wildtype adult DG GCs are small (,0.1 mm2), and of the .270 spines scored (per genotype) we observed that most have round, uniformly shaped, spine heads (Fig. 3a). In contrast, spines in Sema3F-/- and Npn-2-/- mutants are enlarged, vary greatly in shape, and exhibit a 1.7-fold increase in area compared to wild-type spines (Fig. 3a, b and Supplementary Fig. 7a, c, d, f). In spines of mutant mice we observed pre- and postsynaptic components normally associated with wild-type synapses, including electron dense membranous folds in the PSD, vesicle pools near active zones, and docked vesicles associated with presynaptic termini (Fig. 3a, b and Supplementary Fig. 7c, d). However, in adult Sema3F-/- and Npn-2-/- mice we observed a 0,5-fold increase in the fraction of DG GC spines harbouring multiple PSDs (Fig. 3b and Supplementary Fig. 7c, g). Serial section EM reconstructions of several mutant DG GC spines showed that these are perforated PSDs contacted by the same presynaptic terminal (Fig. 3c, d). We found similarly pronounced cortical layer V neuron spine and synaptic morphology defects at the ultrastructural level in both Sema3F2/2 and Npn-22/2 mutants (Supplementary Fig. 8). As spine stability, maturation and number increase with age17,18, we asked whether these abnormalities observed in adult Sema3F-/- and Npn-2-/- mice result from altered spine morphogenesis. Indeed, spines along P21 DG GC dendrites in Npn-2-/- animals already exhibit aberrant morphology similar to that seen in adult Npn-22/2 mutants (Supplementary Fig. 9). These TEM analyses demonstrate that Sema3F and Npn-2 regulate spine morphogenesis and postsynaptic specializations, serving to constrain overall spine number, size and PSD number. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Electron Microscopy Microscopy (generic) Whole-cell patch clamp |
| Annotator(s): | Chiara Verpelli (ORCID:0000-0003-2949-9725) Carlo Sala (ORCID:0000-0003-0662-9523) |
| Lab: | CNR Neuroscience Institute Milan and Dept. of Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy |
| Additional literature: | Similar finding of NRP2 in Sema3F- induced spine remodelling. @ PMID:25143608 |
| SynGO annotation ID: | 1756 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |