Cited by 252Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismCellular transport and secretion

Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission

Murphy-Royal, Ciaran, Dupuis, Julien P, Varela, Juan A, Panatier, Aude, Pinson, Benoît, Baufreton, Jérôme, Groc, Laurent, Oliet, Stéphane H R·2015·Nature Neuroscience

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.

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Crossref · 10.1038/nn.3901

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Authors
Murphy-Royal, C., Dupuis, J. P., Varela, J. A., Panatier, A., Pinson, B., Baufreton, J., Groc, L., & Oliet, S. H. R.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Université de Bordeaux (FR)
Corresponding author
  • Groc, Laurent
  • Oliet, Stéphane H R
Venue
Nature Neuroscience
Published
2015-01-12
Volume
18
Issue
2
Pages
219-226
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2144341669
Cited by
252
References
55
Citations by year
2026: 10 · 2025: 9 · 2024: 16 · 2023: 14 · 2022: 28 · 2021: 23 · 2020: 24 · 2019: 28 · 2018: 23 · 2017: 22 · 2016: 35 · 2015: 20
FWCI
15.49
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
GLT-1, surface diffusion, excitatory postsynaptic currents, synaptic transmission, astrocyte-neuron interaction, glutamate uncaging, hippocampal neurons
MeSH terms
Animals, Astrocytes, Diffusion, Female, Hippocampus, Male, Synaptic Transmission, Rats, Sprague-Dawley, Glutamic Acid, Excitatory Amino Acid Transporter 2, Rats

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