| Annotated protein: | Disks large-associated protein 3 (DAP-3) (PSD-95/SAP90-binding protein 3) (SAP90/PSD-95-associated protein 3) (SAPAP3). Gene symbol: DLGAP3. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q6PFD5 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ DLGAP3 |
| Ontology domain: | Biological Process |
| SynGO term: | modulation of chemical synaptic transmission (GO:0050804) |
| Synapse type(s): | striatum, glutamatergic |
| Annotated paper: | Welch JM, et al. "Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice" Nature. 2007 Aug 23;448(7156):894-900 PMID:17713528 |
| Figure(s): | fig 3; fig 4 |
| Annotation description: | Fig 3 Altered cortico-striatal synaptic transmission in Sapap3-mutant Literal "We found that field excitatory postsynaptic potentials (fEPSPs) were significantly reduced in Sapap3 KO mice compared with wild-type litter mates (Fig. 3b).We next evaluated NMDAR-dependent responses by recording in the presence of an AMPAR antagonist (NBQX) and the NMDAR cofactor glycine, in the absence of magnesium. Surprisingly, in contrast to the reduction we observed in the total fEPSP amplitude, which is dominated by AMPAR transmission under these conditions, the NMDAR-dependent fEPSPs were elevated in Sapap3 KO mice (Fig. 3d, e). These findings indicate a differential effect of Sapap3 deletion on extracellular field potentials that are dependent on AMPAR and NMDAR activity." Fig 4 Altered NMDAR composition of the PSD in striatum Literal: "the level of NR1, the obligatory subunit of the NMDAR, was significantly increased (Fig. 4a, b). 8/11/2017 Pim - Fig.4 is essential and supports the structural role of SAPAP3 in the PSD: "We next examined whether deletion of SAPAP3 affects PSD ultrastructure at cortico-striatal synapses using electron microscopic (EM) analysis to measure the length and thickness of the PSD in the striatum (Fig. 4c, d). We found no significant difference in length of the PSD between SAPAP3-/- and wildtype mice (Fig. 4e). The PSD is reported to exhibit a laminar organization: NMDARs, scaffolding proteins, and signaling proteins reside in the electron-dense layer near the synaptic membrane, while proteins linked to trafficking and the actin cytoskeleton reside in the filamentous fringe towards the cytoplasm32. Accordingly, we independently measured the thickness of the "dense layer" and the fringe "light layer". We found a small but significant reduction in thickness of the dense layer but not the light layer (Fig. 4f, g) of the PSD in striatal synapses in SAPAP3-/- mice, suggesting a subtle defect in the structure of the postsynaptic complex. This finding is consistent with the proposed role of SAPAP3 as a postsynaptic scaffolding protein at excitatory synapses12,17. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Electron Microscopy Field recordings Western blot Biochemical fractionation (generic) |
| 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: | 3690 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |