| Annotated protein: | SH3 and multiple ankyrin repeat domains protein 3 (Shank3) (Proline-rich synapse-associated protein 2) (ProSAP2) (SPANK-2). Gene symbol: SHANK3. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q9JLU4 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ SHANK3 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynapse organization (GO:0099175) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Grabrucker AM, et al. "Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation" EMBO J. 2011 Feb 2;30(3):569-81 PMID:21217644 |
| Figure(s): | Fig. 1, 2, 3, 4 |
| Annotation description: | Fig. 1, in young neurons, overexpressed ProSAP1/Shank2 and ProSAP2/Shank3 increase synapse density, while knockdown by RNAi of ProSAP1/Shank2 and ProSAP2/Shank3 causes a reduction of synapse density. Literal: "When neurons were transfected at DIV 6 and examined at DIV 9 GFP-tagged ProSAP1/Shank2 and ProSAP2/Shank3 efficiently colocalize with the synaptic markers Bassoon and Homer (Figure 1A), while GFP-tagged Shank1 exhibited a limited synaptic localization (Figure 1A). An analysis of synaptic density/unit length of dendrite revealed that GFPtagged ProSAP1/Shank2 and ProSAP2/Shank3 overexpression caused a significant increase in the number of synapses, while GFP-Shank1 overexpression had little effect (Figure 1B). Consistent with a role of these PSD proteins in synapse formation, knockdown of ProSAP/Shank proteins causes a significant reduction in synapse density (Figure 1B; ...)." 23/11/2017 Pim - Shank's is a is a multidomain protein localized to the PSD that is regarded at a scaffold/structural organized of the PSD. - This paper shows that: 1] Shank2 and Shank2 influence synapse formation (Fig.1) 2] Shank2 and Shank2 bind Zn2+. The effect on synapse formation of Shank2 and Shank2 is abolished with overexpression of Zn2+ insensitive mutants (Fig.2). 3] Removal of Zn2+ from neurons caused translocation of Shank2 and Shank2 from PSD to the cytosol. This resulted an increase of the number of synapses that lacked a PSD (Fig.3). 4] Zn2+ depletion causes complete loss of Homer1 (marker protein of PSD) from a subset of synapses (Fig.4). |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression |
| Evidence tracking, Experiment Assay: | Electron Microscopy Confocal |
| 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: | 1963 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |