Annotated protein: | Radixin (ESP10). Gene symbol: RDX. Taxonomy: Mus musculus (Mouse). Uniprot ID: P26043 |
antibody wiki: | |
SynGO gene info: | SynGO data @ RDX |
Ontology domain: | Biological Process |
SynGO term: | regulation of postsynaptic neurotransmitter receptor diffusion trapping (GO:0150054) |
Synapse type(s): | hippocampus |
Annotated paper: | Hausrat TJ, et al. "Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory" Nat Commun. 2015 Apr 20;6:6872 PMID:25891999 |
Figure(s): | Fig 4 and 5 |
Annotation description: | Fig4A-B: GABAAR-α5 was significantly enriched in Rdx-depleted (-/-) synaptosomal fractions compared to WT. While GABAA receptor subunit (GABAAR-α1), as well as pre- and post-synaptic marker proteins remained unchanged. Fig 4C-E: Quantitative immunocytochemistry confirmed enriched GABAAR-α5 signals in (-/-) neurons in apposition to SV2-positive terminal boutons. SV2 signal intensities were comparable between genotypes indicating no difference in synapse densities. To distinguish synaptic from extrasynaptic locations, pixel areas of GABAAR-α5 cluster sizes apposed or non-apposed to the pre-synaptic vesicle marker SV2 were quantified. Fig 4f-g: Extrasynaptic GABAAR-α5 clusters were reduced in Rdx KO neurons compared to wild-type. While an increase in synaptic GABAAR-α5 clusters was observed in Rdx KO neurons. To address whether the alternation between surface membrane diffusion and Rdx-mediated confinement might be the underlying mechanism for the re-distribution of GABAAR-α5 molecules within the plasma membrane, Quantum dot-based -SPT analysis was conducted. Fig 5c: GABAAR-α5 showed alternate diffusion and confinement at extrasynaptic Rdx clusters (depicted in green) and occasionally co-localized with synaptic gephyrin puncta. Fig 5d-e: Overexpression of RdxT564A, which is unable to bind GABAAR-α5, induced a significant increase in the rate of diffusion of extrasynaptic GABAAR-α5 outside of Rdx clusters, compared with overexpression of Rdx-WT. Fig5f-g: GABAAR-α5 showed significantly higher diffusion rates in Rdx (-/-) compared with Rdx (+/+). Together, these findings indicate that the ability of Rdx to anchor GABAAR-α5 extrasynaptically determines whether or not the receptor is free to diffuse across the neuronal cell surface and eventually enters synaptic sites. |
Evidence tracking, Biological System: | Cultured neurons |
Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Antibody (detection) |
Evidence tracking, Experiment Assay: | Confocal unlisted assay type |
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 |
SynGO annotation ID: | 4104 |
Dataset release (version): | 20231201 |
View annotation as GO-CAM model: |