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Glutamate-induced AMPA receptor desensitization increases their mobility and modulates short-term plasticity through unbinding from stargazin

journal contribution
posted on 2023-06-08, 22:41 authored by Audrey Constals, Andrew PennAndrew Penn, Benjamin Compans, Estelle Toulmé, Amandine Phillipat, Sébastien Marais, Natacha Retailleau, Anne-Sophie Hafner, Françoise Coussen, Eric Hosy, Daniel Choquet
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Neuron

ISSN

0896-6273

Publisher

Elsevier

Issue

4

Volume

85

Page range

787-803

Department affiliated with

  • Neuroscience Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2015-10-07

First Compliant Deposit (FCD) Date

2021-03-09

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