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.
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Astroglial cells are the main regulators of cerebral glutamate clearance and metabolism.
“The astroglial cells are the main regulators of cerebral glutamate clearance and metabolism [21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [26]
Glutamine can be reconverted into glutamate for use as a neurotransmitter or energy substrate.
“which in turn can be reconverted into glutamate for use either as a neurotransmitter or energy substrate [21, 22, 23, 24, 25, 26, 27].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [26]
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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
- Licence
- www.springer.com/tdm (tdm)
- 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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