| Annotated protein: | Disrupted in schizophrenia 1 homolog. Gene symbol: DISC1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q811T9 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ DISC1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynapse organization (GO:0099175) |
| Synapse type(s): | cerebral cortex, glutamatergic |
| Annotated paper: | Arguello A, et al. "Dapper antagonist of catenin-1 cooperates with Dishevelled-1 during postsynaptic development in mouse forebrain GABAergic interneurons" PLoS One. 2013 Jun 24;8(6):e67679 PMID:23826333 |
| Figure(s): | Fig.6 |
| Annotation description: | [Fig.3: "Cortical interneurons from constitutive Dact1 mutant mice have fewer excitatory synapses on primary dendrites" Fig.4: "Reduction of excitatory synapses in Dact1 mutant cortical interneurons is cell-autonomous" - "In summary, we found significant reductions in the number of excitatory synapses on cultured cortical interneurons from IDact1-KO mutants, in which only interneurons have lost Dact1, while the number of inhibitory synapses on these dendrites showed a non-significant trend toward reduced numbers. " Fig.5: "Interneuron-specific Dact1 mutant mice (IDact1-KO) have fewer excitatory and inhibitory synapses along cortical interneuron dendrites" - "Interestingly, compared to results obtained in primary culture, in vivo there was a more pronounced and significant decrease (by ~23%) in the number of inhibitory synapses along dendrites of mutant interneurons compared to controls (co-localized inhibitory pre-synaptic (VGAT) and post-synaptic (Gephyrin) puncta: 3.62±0.30 per 10 um in IDact1-KO versus 4.69±0.43 in control, p=0.0471) (Figure 5F, G). For excitatory synapses, the results obtained in vivo were similar to in vitro: there were significant reductions (by ~28%) in the number of excitatory synapses along dendrites of mutant interneurons compared to controls (co-localized excitatory pre-synaptic (VGLUT1) and post-synaptic (PSD95) puncta: 4.62±0.64 per 10 um in IDact1-KO versus 6.42±0.52 in control, p=0.0368) (Figure 5F', G'). "] Fig.6: "Interneuron-specific expression of Dact1, Dvl1, or DISC1 rescues excitatory synapse numbers in IDact1-KO interneurons" - "The cytoplasmic Dvl1 protein is a direct binding partner of Dact1 [21], [34], is a core Wnt pathway component [48], and has been shown to regulate both presynaptic assembly and the postsynaptic formation of excitatory synapses [17], [20]. Similar to rescue with Dact1 itself, recombinant expression of Dvl1 in IDact1-KO interneurons fully rescued excitatory synapse numbers (PSD95 puncta: 5.11±0.57 per 10 um in IDact1-KO + IS-lentivirus (Dvl1), versus 2.85±0.24 in IDact1-KO + IS-lentivirus (empty), p<0.0001) (Figure 6B, C closed bar iii vs. i)." - "Provocatively, recombinant expression of mouse DISC1 in IDact1-KO interneurons partially rescued excitatory synapse numbers (PSD95 puncta: 4.04±0.42 per 10 um in IDact1-KO + IS-lentivirus (DISC1), versus 2.85±0.24 in IDact1-KO + IS-lentivirus (empty), p=0.0143) (Figure 6B, C closed bar v vs. i)." |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | Over-expression |
| Evidence tracking, Experiment Assay: | Confocal |
| Annotator(s): | Pim van Nierop (ORCID:0000-0003-0593-3443) Guus Smit (ORCID:0000-0002-2286-1587) Matthijs Verhage (ORCID:0000-0002-2514-0216) |
| Lab: | Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands |
| SynGO annotation ID: | 2990 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |