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Nat Neurosci. 2015 Feb;18(2):219-26. doi: 10.1038/nn.3901. Epub 2015 Jan 12.

Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission.

Author information

1
1] Neurocentre Magendie, Inserm U862, Bordeaux, France. [2] University of Bordeaux, Bordeaux, France. [3] Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.
2
1] University of Bordeaux, Bordeaux, France. [2] Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France.
3
1] Neurocentre Magendie, Inserm U862, Bordeaux, France. [2] University of Bordeaux, Bordeaux, France.
4
1] University of Bordeaux, Bordeaux, France. [2] Institute for Biochemistry and Cellular Genetics, CNRS UMR 5095, Bordeaux, France.
5
1] University of Bordeaux, Bordeaux, France. [2] Institute of Neurodegenerative Diseases, CNRS UMR 5293, Bordeaux, France.

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.

PMID:
25581361
DOI:
10.1038/nn.3901
[Indexed for MEDLINE]

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