| Annotated protein: | IQ motif and SEC7 domain-containing protein 2. Gene symbol: IQSEC2. Taxonomy: Homo sapiens (Human). Uniprot ID: Q5JU85 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ IQSEC2 |
| Ontology domain: | Biological Process |
| SynGO term: | modulation of chemical synaptic transmission (GO:0050804) |
| Synapse type(s): | Schaffer collateral synapse (CA3->CA1) |
| Annotated paper: | Brown JC, et al. "Bidirectional regulation of synaptic transmission by BRAG1/IQSEC2 and its requirement in long-term depression" Nat Commun. 2016 Mar 24;7:11080 PMID:27009485 |
| Figure(s): | Fig.1, 2, 6, 7, 9, 10 |
| Annotation description: | IQ-ArfGEF/BRAG1/IQSEC2 is a guanine nucleotide exchange factor present in postsynaptic densities of glutamatergic synapses. Overexpression of wildtype BRAG1 in CA1 pyramidal cells in rat hippocampal organotypic slice cultures causes an increase in AMPA receptor mediated responses (Fig.1c, d). Overexpression of a dominant-negative mutant BRAG1-E849K, which lacks Arf-GEF enzymatic activity, still causes an increase in AMPA receptor mediated responses (Fig. 1b), indicating that the enhancement in AMPA receptor responses is unrelated to the enzymatic activity of BRAG1, but rather depends on its C-terminal interactions with PSD-95 (Fig.2). Knock-down (KD) of BRAG1 using different siRNA constructs causes a reduction in AMPA receptor mediated responses (Fig.7a-e) that can be rescued by expression of wildtype BRAG1 (Fig.7f). BRAG1 overexpression increases surface expression levels of GluA2 (Fig. 6), but overexpression or KD of BRAG1 has no effect on LTP generation at the CA3-CA1 SC synapse (Fig.9). However, KD of BRAG1 affects LTD indicating that removal of AMPA receptors is affected in the absence of BRAG1 and this effect depends on the enzymatic Arf-GEF activity of BRAG1 (Fig.10). In summary, these data indicate that BRAG1 modulates the expression levels of AMPA receptors at postsynapses. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp |
| Annotator(s): | Noa Lipstein (ORCID:0000-0002-0755-5899) Cordelia Imig (ORCID:0000-0001-7351-8706) Vincent O'connor (ORCID:0000-0003-3185-5709) Nils Brose (ORCID:0000-0003-0938-8534) |
| Lab: | Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany |
| Additional literature: | Fig.2 of this publication shows the results of an Arf pulldown assay. Co-expression of FLAG-tagged BRAG1 and HA-tagged Arf6 in COS-7 cells caused a strong increase in the amount of GEF-bound Arf6 in comparison to cells that were transfected with Arf6-HA alone. @ PMID:18164504 |
| SynGO annotation ID: | 1077 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |