| Annotated protein: | DOMON domain-containing protein FRRS1L (Ferric-chelate reductase 1-like protein). Gene symbol: FRRS1L. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: D3ZE85 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ FRRS1L |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072) |
| Synapse type(s): | hippocampus |
| Annotated paper: | Brechet A, et al. "AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability" Nat Commun. 2017 Jul 4;8:15910 PMID:28675162 |
| Figure(s): | Figure 6, 7 |
| Annotation description: | FRRS1l regulates the abundance of synaptic and extra-synaptic AMPARs by promoting the biogenesis of AMPARs through interactions with naive tetramers in the ER. shRNA-knockdown or overexpression of FRRS1l in hippocampal neurons decreased or increased, respectively, AMPAR-mediated currents (Figure 6-7). Similar changes in EPSC amplitude were observed in mossy fiber cells (MC), interneurons, and CA3 pyramidal cells from rat hippocampal slices transduced with sh-FRRS1l or FRRS1l cDNA (Figure 7). "Bi-allelic mutations in the human FRRS1L gene cause intellectual disability." Figure 3, autosomal-recessive form of intellectual disability. The stability of FRRS1l protein as well as its co-assembly with AMPARs was largely affected by expression of ID-associated FRRS1l mutants in heterologous cells (Figure 4d). Localization: Electron micrograph showing FRRS1L (immunogold) localizes to ER in soma of CA1 pyramidal neurons (Figure 5b). Only 3.9% of FRRS1L particles were found on or near the plasma membrane. These data together with confocal microscopy analysis (adult rat hippocampal slices, hilar region Fig 5a) show FRRS1L localizes primarily to the ER in soma or proximal dendrites in hippocampal neurons. FRRS1L does not appear to be localized to synapses. FRRS1L has a putative TM helix (uniprot D3ZE85 or B1AXV0, mouse and rat) so it is likely an integral component of ER. 18/01/2018 Pim - In figures 7 it is shown that the amount of AMPARs in the PSD is reduced. The term 'regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696)' was not awarded because in figure 6 it is shown that "Decrease or increase of currents mediated by synaptic and extra-synaptic AMPARs upon knockdown and exogenous (over)expression of FRRS1l in distinct types of hippocampal neurons.". The effect on AMPAR levels in the PSD is downstream of the number of AMPARs in the membrane. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression |
| Evidence tracking, Experiment Assay: | 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 |
| SynGO annotation ID: | 2069 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |