期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms7872
关键词
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资金
- University Medical Center Hamburg-Eppendorf (UKE)
- German Research Foundation (DFG) [KN556/4-1, KN556/4-2, KN556/6-1, GRK1459]
- Chica and Heinz Schaller Foundation
- Hamburg Landesforschungsforderung (LFF) program
- ERC Plastinhib
- ANR Synaptune
- Program 'Investissements d'Avenir' [ANR-10-LABX-54 MemoLife]
- EMBO fellowship
- UKE fellowship Forschungsforderung Fakultatsmittel (FFM)
- MRC [MR/K005537/1] Funding Source: UKRI
- Medical Research Council [MR/K005537/1] Funding Source: researchfish
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. GABA(A) receptors containing alpha 5-subunits (GABA(A)R-alpha 5) 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 GABA(A)R-alpha 5 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 GABA(A)Rs.
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