title: Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission.
abstract: Control of the glutamate time course in the synapse is crucial for excitatory transmission. This process is mainly ensured by astrocytic transporters, high expression of which is essential to compensate for their slow transport cycle. Although molecular mechanisms regulating transporter intracellular trafficking have been identified, the relationship between surface transporter dynamics and synaptic function remains unexplored. We found that GLT-1 transporters were highly mobile on rat astrocytes. Surface diffusion of GLT-1 was sensitive to neuronal and glial activities and was strongly reduced in the vicinity of glutamatergic synapses, favoring transporter retention. Notably, glutamate uncaging at synaptic sites increased GLT-1 diffusion, displacing transporters away from this compartment. Functionally, impairing GLT-1 membrane diffusion through cross-linking in vitro and in vivo slowed the kinetics of excitatory postsynaptic currents, indicative of a prolonged time course of synaptic glutamate. These data provide, to the best of our knowledge, the first evidence for a physiological role of GLT-1 surface diffusion in shaping synaptic transmission.
authors.affiliation: 1] Neurocentre Magendie, Inserm U862, Bordeaux, France. [2] University of Bordeaux, Bordeaux, France. [3] Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.
authors.forename: Ciaran
authors.initials: C
authors.lastname: Murphy-Royal
authors.affiliation: 1] University of Bordeaux, Bordeaux, France. [2] Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.
authors.forename: Julien P
authors.initials: JP
authors.lastname: Dupuis
authors.affiliation: 1] University of Bordeaux, Bordeaux, France. [2] Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Varela
authors.affiliation: 1] Neurocentre Magendie, Inserm U862, Bordeaux, France. [2] University of Bordeaux, Bordeaux, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Panatier
authors.affiliation: 1] University of Bordeaux, Bordeaux, France. [2] Institute for Biochemistry and Cellular Genetics, CNRS UMR 5095, Bordeaux, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Pinson
authors.affiliation: 1] University of Bordeaux, Bordeaux, France. [2] Institute of Neurodegenerative Diseases, CNRS UMR 5293, Bordeaux, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Baufreton
authors.affiliation: 1] University of Bordeaux, Bordeaux, France. [2] Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Groc
authors.affiliation: 1] Neurocentre Magendie, Inserm U862, Bordeaux, France. [2] University of Bordeaux, Bordeaux, France.
authors.forename: Stéphane H R
authors.initials: SH
authors.lastname: Oliet
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004058:Diffusion; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid