| Annotated protein: | Disks large-associated protein 4 (DAP-4) (PSD-95/SAP90-binding protein 4) (SAP90/PSD-95-associated protein 4) (SAPAP-4). Gene symbol: DLGAP4. Taxonomy: Mus musculus (Mouse). Uniprot ID: B1AZP2 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ DLGAP4 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of synapse maturation (GO:0090128) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Schob C, et al. "Cognitive impairment and autistic-like behaviour in SAPAP4-deficient mice" Transl Psychiatry. 2019 Jan 16;9(1):7 PMID:30664629 |
| Figure(s): | Figure 2, 3 |
| Annotation description: | Figure 1: SAPAP4 (DLGAP4) -deficient mice were generated. Figure 2: Confocal imaging showed the number of branching points and path length of apical dendrites was reduced in KO mice as compared to control, with only minor non-significant effect on basal dendrites. There was a slight but significant decrease in the fraction of stubby spines in KO mice, while the relative amounts of mushroom-type and thin spines increased to some extent but not significantly (Fig. 2g). The mean spine density remained unchanged (Fig. 2h). EM corroborated that mean spine density was unchanged, but did find an increase of 70% for the mean area covered by the PSD. By focussing mainly on scaffold proteins and receptor subunits, we observed that the in vivo loss of SAPAP4 does not noticeably alter the molecular composition of the PSD (Fig. 2m). Noteworthy, we did not observe a compensatory increase in the level of other family members. By trend, postsynaptic levels of the NMDAR subunit GluN1 were found to be enlarged. Authors summarised: "Taken together, our findings show that SAPAP4 plays an important role in regulating PSD size, while exhibiting only minor effects on spine density and shape." Figure 3: electrophysiology of CA1 pyramidal neurons in acute hippocampal slices showed impaired synaptic transmission, plasticity and network activity in SAPAP4-deficient mouse brains. LTD was impaired in KO mice, while LTP was not. A significantly higher GluN2B/GluN2A ratio was observed. Authors conclude: "The increased GluN2B/GluN2A ratio at SAPAP4-deficient synapses suggests that SAPAP4 is critically involved in molecular events underlying NMDAR subunit transition and maturation of excitatory synapses." Importantly, authors remark that "While these data may suggest a synaptic function of SAPAP4 that is distinct from that of SAPAP2 and SAPAP3, they may as well reflect regional differences within the brain, such as varying expression levels of other PSD components." |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Electron Microscopy Confocal |
| Annotator(s): | Frank Koopmans (ORCID:0000-0002-4973-5732) 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 |
| Additional literature: | "The present study shows that the loss of SAPAP4 in mice leads to synaptic defects at molecular and cellular levels including reduced spine density, decreased levels of PSD95, GluR1, and GluR2 in the PSD, and surprisingly, increased level of SHANK3 in the PSD." "The synaptic defects in Sapap4 KO mice reported here provide further evidence to support the important role of this scaffolding complex in synaptic development and function. A surprising finding is the elevated level of SHANK3 in the PSD of Sapap4 KO mice, suggesting that regulation of synaptic localization of PSD95 and SHANK3 is not always directly linked, different from depicted in the PSD95-SAPAP-SHANK model (Kim and Sheng 2004; Funke et al. 2005)." "Together, our findings indicate that SAPAP4 plays an important role in synaptic structure and function and suggest a unique role for SAPAP4 in regulating circuit function" @ PMID:35368073 |
| SynGO annotation ID: | 4860 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |