| Annotated protein: | Glycogen synthase kinase-3 beta (GSK-3 beta) (EC 2.7.11.26) (Serine/threonine-protein kinase GSK3B) (EC 2.7.11.1). Gene symbol: GSK3B. Taxonomy: Homo sapiens (Human). Uniprot ID: P49841 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ GSK3B |
| Ontology domain: | Biological Process |
| SynGO term: | presynaptic modulation of chemical synaptic transmission (GO:0099171) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Zhu LQ, et al. "Activation of glycogen synthase kinase-3 inhibits long-term potentiation with synapse-associated impairments" J Neurosci. 2007 Nov 7;27(45):12211-20 PMID:17989287 |
| Figure(s): | Fig 1G and H, Fig.3, Fig. 4A and B |
| Annotation description: | Fig 1G and H, Overexpression of GSK3B inhibits LTP in CA3 neurons Literal: "To induce and record LTP, we placed a stimulating electrode in the perforant path and a recording electrode in CA3 region of rat hippocampus through a stereotaxic instrument.... To confirm the role of GSK-3, we transiently expressed wtGSK-3beta, dnGSK-3beta, or pcDNA into the rat brains. The efficient expression of GSK-3beta (see Fig. 4A, HA-tag) in the region of CA3 (Fig. 1A, black square) was confirmed by examination using a fluorescence microscope immediately after the electrophysiological recording (26 h after the transfection). After HFS, the PS amplitude increased to approximately 2.2- to 2.6-fold of the basal level in rats expressing pcDNA, whereas the increase was only approximately 1.4- to 1.6-fold of the basal level in rats overexpressing wtGSK-3beta. The levels of PS amplitude were restored to approximately 2.0- to 2.3-fold of the normal basal levels in rats expressing dnGSK-3beta and in rats expressing wtGSK-3beta with simultaneous treatment of SB216763 (Fig. 1G). Similar results were also observed by EPSP analysis (Fig. 1H). Together, these data strongly suggest that upregulation of GSK-3beta inhibits LTP." Fig. 4A and B, overexpression of GSK3B reduces expression of SynI. Literal "To explore whether GSK-3 affects SynI, we transiently expressed wtGSK-3beta, dnGSK-3beta, or pcDNA in the hippocampal CA3 region of the rats. LTP was recorded as indicated in Figure 1A at 24 h after the transfections, the level of SynI was measured by immunofluorescence staining. SynI was detected in both the cytoplasm and the processes of neurons in the pcDNA-transfected region of the brain slices. The staining of SynI was almost completely diminished in neurons expressing wtGSK-3beta and was significantly restored when dnGSK-3beta was expressed (Fig. 4A). These results indicate that activation of GSK-3 inhibits the expression of SynI after induction of LTP. To explore whether GSK-3 affects SynI independent of LTP, we measured the expression of SynI in 8 d in vitro (DIV) primary hippocampal neurons without potentiation treatment. Compared with nontransfected neurons in the same visual view, SynI staining became much weaker in neurons overexpressing wtGSK-3beta-HA (Fig. 4B, arrowheads). We selected 8-12 neurons from four independent experiments and analyzed the staining of Syn I in GSK-3beta-positive and -negative cells. We found that the staining intensity of Syn I in GSK-3beta-positive cells decreased to 35% of the control cells, in which GSK-3beta (HA-tag) was negative ( p < 0.01)." 9/11/2017 Pim - The authors propose a model for GSK3B action, where GSK3B acts exclusively in the presynaptic compartment. Postsynaptic effects are all attributed to perturbation of presynaptic GSK3B. This contradicts other papers that report a exclusive PSD localization of GSK3B in cortex (ticket #1787 and #1789). Because the authors postulate this model I refrain from making annotations of the postsynaptic effects. - The authors show that GSK3B activity regulates the expression level of SynI. This in turn can explain the effects on the SV release. However, since no further detail is given on the cause of the increased expression (more synthesis, chaperonne function, less degradation) I cannot incorporate this in the annotation (term missing from SynGO slim). Instead, only the (possibly) secondary effects on SV release are annotated. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Over-expression Antagonist / agonist |
| Evidence tracking, Experiment Assay: | Confocal Field recordings Biochemical fractionation (generic) ELISA |
| 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 |
| SynGO annotation ID: | 1798 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |