| Annotated protein: | Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86). Gene symbol: HSP90AA1. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: P82995 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ HSP90AA1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072) |
| Synapse type(s): | hippocampus |
| Annotated paper: | Gerges NZ, et al. "Independent functions of hsp90 in neurotransmitter release and in the continuous synaptic cycling of AMPA receptors" J Neurosci. 2004 May 19;24(20):4758-66 PMID:15152036 |
| Figure(s): | Fig1,3 and 5 |
| Annotation description: | Fig1A: Addition of radicicol, a cell-permeable specific inhibitor of hsp90, produced a rapid decrease in AMPA receptor-mediated currents. Addition of an equivalent amount of the radicicol vehicle (0.1% DMSO) did not alter AMPA transmission. Fig1B: Changes in response amplitude shown in Figure 1A were not attributable to systematic variations in access resistance during the recordings. Fig3: Slices preincubated in radicicol showed a significant decrease in AMPA/NMDA ratio compared with naive slices or with slices treated with vehicle (DMSO). Geldanamycin, a chemically different inhibitor of hsp90 also showed significantly reduced AMPA/NMDA ratios. Fig5: Recombinant homomeric AMPA receptor subunit (GluR2 R586Q) was expressed in organotypic hippocampal slices. The mutation R586Q at the channel pore prevents the receptor from conducting outward currents at positive membrane potentials (inward rectification). The synaptic delivery of the recombinant receptor can be detected as an increase in the ratio of the AMPA receptor-mediated response at -60 mV versus the response at +40 mV (rectification index). In the absence of radicicol, expression of the recombinant receptor produced inward rectification (increase in the rectification index) compared to control indicating the delivery of the homomeric receptor. Thirty-minute incubation with radicicol on slices expressing GluR2 (R586Q) blocked this rectification because GluR2 receptors might be constitutively cycling in and out of synapses. This suggests the probable role of hsp90 for either the synaptic reinsertion of AMPA receptors during their continuous cycling or their stability once inserted at synapses. 19/01/2021 Dnyanada: PMID:10478836 demonstrates specificity of the Hsp90 inhibitor, radicicol. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Antagonist / agonist |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp |
| Annotator(s): | Dnyanada Sahasrabudhe (ORCID:0000-0003-2916-7616) 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: | Cell lysates were extracted with biotinylated radicicol bound to streptavidin beads and detected by immunoblotting. The specificity of Hsp90 purification is demonstrated by the absence of binding of the protein to streptavidin beads alone and competition of binding by soluble radicicol. @ PMID:10478836 |
| SynGO annotation ID: | 4131 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |