title: Glutamate-induced AMPA receptor desensitization increases their mobility and modulates short-term plasticity through unbinding from Stargazin.
abstract: 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.
authors: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.
authors: Audrey
authors: A
authors: Constals
authors: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.
authors: Andrew C
authors: AC
authors: Penn
authors: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.
authors: Benjamin
authors: B
authors: Compans
authors: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.
authors: Estelle
authors: E
authors: Toulmé
authors: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.
authors: Amandine
authors: A
authors: Phillipat
authors: Bordeaux Imaging Center, UMS 3420 CNRS, US4 INSERM, University of Bordeaux, F-33000 Bordeaux, France.
authors: Sébastien
authors: S
authors: Marais
authors: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.
authors: Natacha
authors: N
authors: Retailleau
authors: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.
authors: Anne-Sophie
authors: AS
authors: Hafner
authors: University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France; CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.
authors: Françoise
authors: F
authors: Coussen
authors: 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: eric.hosy@u-bordeaux.fr.
authors: Eric
authors: E
authors: Hosy
authors: 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: daniel.choquet@u-bordeaux.fr.
authors: Daniel
authors: D
authors: Choquet
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011487:Protein Conformation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D055366:Synaptic Potentials / Q000187:drug effects / Q000235:genetics; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D015220:Calcium Channels; D018683:Excitatory Amino Acid Agents; D018698:Glutamic Acid; D008164:Luminescent Proteins; D018091:Receptors, AMPA; C491911:Cacng2 protein, rat; C104722:glutamate receptor ionotropic, AMPA 2