Hausrat, TJ;
Muhia, M;
Gerrow, K;
Thomas, P;
Hirdes, W;
Tsukita, S;
Heisler, FF;
... Kneussel, M; + view all
(2015)
Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory.
Nature Communications
, 6
, Article 6872. 10.1038/ncomms7872.
Preview |
Text
Smart_Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory.pdf Download (2MB) | Preview |
Abstract
Neurotransmitter receptor density is a major variable in regulating synaptic strength. Receptors rapidly exchange between synapses and intracellular storage pools through endocytic recycling. In addition, lateral diffusion and confinement exchanges surface membrane receptors between synaptic and extrasynaptic sites. However, the signals that regulate this transition are currently unknown. GABAA receptors containing α5-subunits (GABAAR-α5) concentrate extrasynaptically through radixin (Rdx)-mediated anchorage at the actin cytoskeleton. Here we report a novel mechanism that regulates adjustable plasma membrane receptor pools in the control of synaptic receptor density. RhoA/ROCK signalling regulates an activity-dependent Rdx phosphorylation switch that uncouples GABAAR-α5 from its extrasynaptic anchor, thereby enriching synaptic receptor numbers. Thus, the unphosphorylated form of Rdx alters mIPSCs. Rdx gene knockout impairs reversal learning and short-term memory, and Rdx phosphorylation in wild-type mice exhibits experience-dependent changes when exposed to novel environments. Our data suggest an additional mode of synaptic plasticity, in which extrasynaptic receptor reservoirs supply synaptic GABAARs.
| Type: | Article |
|---|---|
| Title: | Radixin regulates synaptic GABAA receptor density and is essential for reversal learning and short-term memory |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncomms7872 |
| Publisher version: | http://dx.doi.org/10.1038/ncomms7872 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit: http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Animals, Cytoskeletal Proteins, Electrophysiological Phenomena, Gene Expression Regulation, Hippocampus, Learning, Membrane Proteins, Mice, Knockout, Receptors, GABA-A, Synapses, Cell signalling, Short-term memory, Synaptic plasticity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1492433 |
Archive Staff Only
 |
View Item |
