| Annotated protein: | Protein Wnt-5a. Gene symbol: WNT5A. Taxonomy: Mus musculus (Mouse). Uniprot ID: P22725 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ WNT5A |
| Ontology domain: | Biological Process |
| SynGO term: | postsynaptic modulation of chemical synaptic transmission (GO:0099170) |
| Synapse type(s): | hippocampus, glutamatergic Schaffer collateral synapse (CA3->CA1) |
| Annotated paper: | Chen CM, et al. "Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice" Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E619-E628 PMID:28069946 |
| Figure(s): | fig 2a-g, 4a-j; s2e&f, s3; movies s1&s2 |
| Annotation description: | From Results section: "Quantification of dendritic spine densities also revealed a significant reduction (31.5% decrease) in 6-mo-old CaMKII-Wnt5afl/fl mice compared with controls (Fig. S2 E and F)." (...) "Together, these results indicate a requirement for Wnt5a in the maintenance of dendrite arbors and spine densities in adult CA1 neurons." "We observed that basal synaptic transmission is normal in CaMKII-Wnt5afl/fl mice at 3 mo but not at 6 mo, consistent with impaired dendritic structures at this age (Fig. 2 A-D). We also measured the probability of synaptic release at presynaptic sites by paired pulse facilitation (PPF) analyses and found that PPF was comparable between CaMKII-Wnt5afl/fl mice and control littermates at both 3 and 6 mo of age (Fig. S3). The normal presynaptic properties in Wnt5a-deficient mice suggests that Wnt5a acts primarily at postsynaptic sites." "To assess the role of Wnt5a in NMDA receptordependent long-term potentiation (LTP), an electrophysiological correlate of strengthening of synaptic transmission, we used θ-burst stimulation to induce LTP at Schaffer collateral-CA1 synapses in 3-mo-old mice." (...) "The impairment in LTP detected at 3 mo in CaMKII-Wnt5afl/fl mice when neuronal structure and basal synaptic transmission are still intact, suggests that synaptic plasticity is more susceptible to the loss of Wnt5a." (...) "Taken together, these results indicate a specific role for Wnt5a in the potentiation of synaptic efficacy." "We next assessed the Wnt-calcium pathway, where Wnt ligands promote an increase of cytoplasmic Ca2+ (49, 50). Strikingly, Wnt5a treatment acutely elicited a calcium response in 92% of cultured rat hippocampal neurons transfected with GCaMP3, whereas only 43% of neurons responded to control treatment. Furthermore, the number of calcium transients was fivefold higher in Wnt5a-treated neurons (Fig. 4 A-C and Movies S1 and S2)." "Using a phospho-specific antibody that detects activated CaMKII (threonine 286 phosphorylation on CaMKIIα and T287 on CaMKIIβ) (53), we found a pronounced attenuation of phosphorylated CaMKIIα (59% decrease) and CaMKIIβ (57% decrease) in CaMKII-Wnt5afl/fl mice (Fig. 4 D and E). CaMKII-mediated phosphorylation of the GluA1 subunit of AMPA-type glutamate receptors at a critical serine 831 site (54, 55) has been functionally linked to synaptic plasticity and retention of spatial memory in mice (56, 57). We found a marked decrease in phospho-S831-GluA1 in postsynaptic density fractions from the mutant hippocampus (Fig. 4 D and E). These results suggest decreases in phosphorylation of CaMKII and GluA1 as the molecular underpinnings for the impairments in synaptic plasticity and spatial memory in CaMKII-Wnt5afl/fl mice." "Phosphorylation of CaMKIV and CREB were significantly reduced in nuclear fractions from 3-mo-old CaMKII-Wnt5afl/fl hippocampal tissues (Fig. 4 F and G). Because Wnt5a deletion altered nuclear CREB phosphorylation, we assessed levels of several synaptic proteins (Fig. S5 D and E) and found that only GluN1, the obligatory NMDA receptor subunit, was decreased (Fig. 4 H-J)" (...) "These results reveal an unexpected role for Wnt5a in enhancing GluN1 transcription through a noncanonical pathway that involves calcium-CaMKII-CREB activation." |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal Field recordings |
| 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: | 2986 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |