Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission
Nat Neurosci. 2015-01-12; 18(2): 219-226
DOI: 10.1038/nn.3901
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1. 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.
Murphy-Royal C(1), Dupuis JP(2), Varela JA(2), Panatier A(3), Pinson B(4),
Baufreton J(5), Groc L(2), Oliet SH(3).
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.
Comment in
Nat Neurosci. 2015 Feb;18(2):166-8.
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.
DOI: 10.1038/nn.3901
PMID: 25581361 [Indexed for MEDLINE]