Annotated protein: | Disks large homolog 4 (Postsynaptic density protein 95) (PSD-95) (Synapse-associated protein 90) (SAP-90) (SAP90). Gene symbol: DLG4. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: P31016 |
antibody wiki: | |
SynGO gene info: | SynGO data @ DLG4 |
Ontology domain: | Biological Process |
SynGO term: | structural constituent of postsynaptic density (GO:0098919) |
Synapse type(s): | hippocampus, glutamatergic |
Annotated paper: | Chen X, et al. "PSD-95 is required to sustain the molecular organization of the postsynaptic density" J Neurosci. 2011 Apr 27;31(17):6329-38 PMID:21525273 |
Figure(s): | Figures 3-6, Table 1 |
Annotation description: | This paper combines immunolabeling with EM tomography to show that in cultured hippocampal neurons the "the orthogonal molecular scaffold constructed from PSD-95-containing vertical filaments and their associated horizontal elements is essential for sustaining the three-dimensional molecular organization of the PSD." Fig.3: "Patchy loss at the PSD correlates with PSD-95 knockdown" Cultured hippocampal neurons expressing PSD-95 shRNA showed loss of patches of material in from the PSD, thinning and shortening of the PSD compared to control cells. Fig. 4: "Knockdown of PSD-95 results in patchy loss of vertical filaments along with other components of the PSD." Table 1, Fig. 4C, 4F, 5G: "The number of AMPAR-type structures in the peripheral zones decreased significantly" following PSD-95 knockdown. NMDAR structures were largely unaffected in knockdown neurons (Fig. 5C, 5G). Fig. 5F, 6: Horizontal elements were less frequent in peripheral zones of the PSD following PSD-95 knockdown. In these regions, they contacted vertical elements that were not attached to major membrane structures and occurred in regions of patchy PSD loss. Horizontal elements appeared as filaments and more complex shapes, "indicating a heterogenous molecular population." Fig.2F-G: Validation of shRNA knockdown of PSD95 in hippocampal cultures by western blot. Fig.2B-C: Validation of shRNA knockdown of PSD95 in hippocampal cultures by immunostaining. |
Evidence tracking, Biological System: | Intact tissue Cultured neurons |
Evidence tracking, Protein Targeting: | RNAi / shRNA Antibody (detection) |
Evidence tracking, Experiment Assay: | Electron Microscopy Confocal |
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: | Validation of antibodies used for immunogold labeling in Zheng CY et al (PMID 20357126). @ PMID:10648730 Use EM tomography to examine molecular organization of glutamatergic synapses in primary rat hippocampal cultures. Define vertical and horizontal filaments in the PSD which are functionally characterized by Chen X et al 2011 ( PMID 21525273). @ PMID:18326622 |
SynGO annotation ID: | 2375 |
Dataset release (version): | 20231201 |
View annotation as GO-CAM model: |