Glutamate-induced AMPA receptor desensitization increases their mobility and modulates short-term plasticity through unbinding from Stargazin.
Neuron. 2015-02-01; 85(4): 787-803
DOI: 10.1016/j.neuron.2015.01.012
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1. Neuron. 2015 Feb 18;85(4):787-803. doi: 10.1016/j.neuron.2015.01.012. Epub 2015
Feb 5.
Glutamate-induced AMPA receptor desensitization increases their mobility and
modulates short-term plasticity through unbinding from Stargazin.
Constals A(1), Penn AC(1), Compans B(1), Toulmé E(1), Phillipat A(1), Marais
S(2), Retailleau N(1), Hafner AS(1), Coussen F(1), Hosy E(3), Choquet D(4).
Author information:
(1)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for
Neuroscience, UMR 5297, F-33000 Bordeaux, France.
(2)Bordeaux Imaging Center, UMS 3420 CNRS, US4 INSERM, University of Bordeaux,
F-33000 Bordeaux, France.
(3)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for
Neuroscience, UMR 5297, F-33000 Bordeaux, France. Electronic address:
.
(4)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for
Neuroscience, UMR 5297, F-33000 Bordeaux, France; Bordeaux Imaging Center, UMS
3420 CNRS, US4 INSERM, University of Bordeaux, F-33000 Bordeaux, France.
Electronic address: .
Short-term plasticity of AMPAR currents during high-frequency stimulation depends
not only on presynaptic transmitter release and postsynaptic AMPAR recovery from
desensitization, but also on fast AMPAR diffusion. How AMPAR diffusion within the
synapse regulates synaptic transmission on the millisecond scale remains
mysterious. Using single-molecule tracking, we found that, upon glutamate
binding, synaptic AMPAR diffuse faster. Using AMPAR stabilized in different
conformational states by point mutations and pharmacology, we show that
desensitized receptors bind less stargazin and are less stabilized at the synapse
than receptors in opened or closed-resting states. AMPAR mobility-mediated
regulation of short-term plasticity is abrogated when the glutamate-dependent
loss in AMPAR-stargazin interaction is prevented. We propose that transition from
the activated to the desensitized state leads to partial loss in AMPAR-stargazin
interaction that increases AMPAR mobility and allows faster recovery from
desensitization-mediated synaptic depression, without affecting the overall
nano-organization of AMPAR in synapses.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neuron.2015.01.012
PMID: 25661182 [Indexed for MEDLINE]