Annotated protein:Protein Wnt-5a. Gene symbol: WNT5A. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q9QXQ7
antibody wiki:
SynGO gene info:SynGO data @ WNT5A
Ontology domain:Biological Process
SynGO term:modulation of chemical synaptic transmission (GO:0050804)
Synapse type(s):hippocampus, glutamatergic
Schaffer collateral synapse (CA3->CA1)
Annotated paper:Parodi J, et al. "Wnt5a inhibits K(+) currents in hippocampal synapses through nitric oxide production" Mol Cell Neurosci. 2015 Sep;68:314-22 PMID:26311509
Figure(s):fig 1, 2 & 3; table 1
Annotation description:"We report here that Wnt5a signaling inhibits a voltage-gated K+ current through an increase in NO production in hippocampal neurons."

From Results section:

"After 3min ofWnt5a treatment, theNOproduction increased by 50% (Fig. 1A, black circles)." (...) "After 3 min of bath application ofWnt5a, we observed a significant and reversible reduction in the voltage-gated K+ current amplitude (Fig. 1B).Moreover, the effect ofWnt5awas voltage-dependent: it was significantly different from the control values at test pulses of +10mV (p b 0.05), and the degree of current inhibition was increased atmore depolarized values (p b 0.01). Amaximuminhibition of approximately 50% of the K+ current (when compared to the control conditions) was achieved at +40 mV (Fig. 1B). No further inhibition of the K+ current was achieved by increasing the Wnt5a concentration. Indeed, this Wnt5a-sensitive current showed a voltage-dependent current-voltage relationship (obtained by current traces subtraction in both the absence and presence of Wnt5a), with an apparent value of voltage activation between-20 mV and-10 mV (Fig. 1B), suggesting that thisWnt5a-sensitive current has a strong component consisting of a delayed rectifier K+ current (Fig. 1C arrow). This effect ofWnt5a was reversible, as indicated by the restoration of current responses after 3 min of washing out the ligand (Fig. 1D, wash-out)."

"The Wnt5a signaling-dependent inhibition of the voltage-gated K+ currents (Fig. 2A,white circles)was abolished by co-treatmentwith soluble 25 μM of Frizzled-related protein 2 (sFRP-2) (Fig. 2, gray circle), a Wnt antagonist (Rattner et al., 1997) that binds Wnt ligands and prevents their interaction with the cellular receptors." (...) "The inhibitory effect of Wnt5a on the voltage-gated K+ currents (Fig. 2A, white circles) was not observed in the presence of 1 μMof 7-NI (Fig. 2A, light gray circles), and the K+ currents were very similar to those of the control (Fig. 2A, black circles)." (...) "Wnt5a evoked a 2-fold increase in the miniature current activity recorded from hippocampal slices (Fig. 2B), an effect that was prevented by the presence of either sFRP-2 or 7-NI (Fig. 2C)." (...) "Here, we show that by enhancing NO production, Wnt5a is responsible for the diminished amplitude of the K+ current, inducing an increase in the miniature activity in cultured hippocampal neurons. Moreover, Wnt5a is responsible for the diminished amplitude of this K+ current in cultured hippocampal neurons, a change that could lead to the increased miniature activity observed in hippocampal slices. Thus, the addition of increasing concentrations of 7-NI eventually inhibits the production of NO (Table 1), restoring the K+ channel activity to the control levels and the miniature events to the resting values. Therefore, our results suggest thatWnt5a signaling may regulate neuron excitability by a mechanism that involves NO-mediated K+ current inhibition of the hippocampal Kv 3.1 and Kv 3.2 channels."

"Wnt5a treatment induced a fast increase "early" in the fEPSP slope (Fig. 3A: black circles); this effect was prevented by the co-incubation of the Wnt ligand with the NOS inhibitor 7-NI (Fig. 3A, upper graph: gray circles). The specificity of the Wnt5a effect was analyzed using sFRP-2. Co-treatment with the ligand and sFRP-2 blocked the effect of Wnt5a on the fEPSP slope to the same extent as 7-NI and to approximately the level of the control; both inhibitors significantly blocked the Wnt activity (Fig. 3A: lower graph, *p b 0.05). This early effect occurred after Wnt5a increased NO production (see Fig. 1A) and decreased K+ currents (Fig. 1B, C). Therefore, 7-NI must have blocked the Wnt5a effect during the "early" stage of treatment with the ligand because when Wnt5a had induced the first increase in fEPSP, the subsequent 7-NI treatment was unable
to prevent or revert the effect ofWnt5a (Fig. 3B, upper, gray circle). Similar results were observed during the "late" stage of the treatment (Fig. 3B, lower, light gray bar)."
Evidence tracking, Biological System:Intact tissue
Cultured neurons
Evidence tracking, Protein Targeting:Antagonist / agonist
Evidence tracking, Experiment Assay:Whole-cell patch clamp
Field recordings
Photoconversion assay
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:3086
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology