| Annotated protein: | Disks large homolog 1 (Synapse-associated protein 97) (SAP-97) (SAP97). Gene symbol: DLG1. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q62696 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ DLG1 |
| Ontology domain: | Biological Process |
| SynGO term: | neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645) |
| Synapse type(s): | hippocampus, glutamatergic cerebral cortex, glutamatergic |
| Annotated paper: | Rumbaugh G, et al. "Synapse-associated protein-97 isoform-specific regulation of surface AMPA receptors and synaptic function in cultured neurons" J Neurosci. 2003 Jun 1;23(11):4567-76 PMID:12805297 |
| Figure(s): | Figures 3-7 |
| Annotation description: | SAP97 belongs to the PSD-MAGUK family of scaffolding proteins and binds directly to the GluA1 subunit of AMPARs. SAP97 regulation of AMPAR synaptic targeting and spine morphology is modulated by alternative splicing. Figure 3. Overexpression of SAP97 causes the enlargement of dendritic spines. DIV 15 cortical neurons transfected with eGFP and myc-SAP97. Figure 4. Expression of GFP-SAP97 enhances expression of surface AMPARs and synaptic transmission in primary cultured neurons. Hippocampal neurons (DIV 10-14) transfected with GFP-SAP97 were live-labeled with N-terminal GluA1 antibodies; overexpression of GFP-SAP97 increased surface GluA1 staining as well as the size of surface GluA1 clusters of AMPARs compared to neighboring, untransfected cells (Fig. 4A-B). DIV 14-16 cultured cortical neurons expressing GFP-SAP97 exhibited a strong enhancement in the frequency of mEPSCs and a slight but not significant decrease in mEPSC amplitude compared with eGFP-expressing neurons (Fig. 4C). Older neurons (DIV 28) expressing GFP-SAP97 showed no significant difference in mEPSC frequency or amplitude from controls (Fig. 4D). "There was a trend toward an increase in mEPSC frequency, but it did not reach a level of significance." Figure 5. A protein 4.1 binding motif and f-actin are required for GFP-SAP97 targeting to spines. The hook region of SAP97 is a site of alternative splicing and a critical region required for targeting of SAP97 to dendritic spines. Examined spatial distribution of GFP-SAP97 deletion constructs in cortical neurons (DIV 14). GFP-SAP97-I2 showed diffuse localization indistinguishable from GFP-SAP97ΔI3, where GFP-SAP97 (I3) was concentrated in dendritic spines. Fig. 6C-E: Confirmed the I3 isoform of SAP97 is expressed in cultured cortical neurons (DIV 14) by reverse transcription (RT)-PCR. SAP97-I2 and -I5 splice variants were also found. Fig. 7: "The I3 sequence is necessary for SAP97-mediated increases in surface AMPA receptors and alterations in mEPSC frequency." Analysis of surface GluA1-AMPARs and mEPSCs in DIV 10 hippocampal neurons transfected with GFP-SAP97ΔI3. additional info: Figs. 1-2. Subcellular localization of endogenous and GFP-SAP97 in primary neurons. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Over-expression Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp |
| Annotator(s): | Hana Goldschmidt (ORCID:0000-0002-5676-366X) Richard Huganir (ORCID:0000-0001-9783-5183) |
| Lab: | Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA and Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205, USA |
| Additional literature: | Unlike PSD-93 and PSD-95, SAP97 can binds directly to the GluA1 subunit of AMPARs. @ PMID:9677374 PMID:20133708 PMID:19858198 |
| SynGO annotation ID: | 2635 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |