Surface diffusion of the astrocytic glutamate transporter glt-1 shapes synaptic transmission
Traffic membranaire des transporteurs du glutamate astrocytaires GLT-1
Résumé
A classic understanding of neurotransmitter clearance at glutamatergic synapses is that, in order to ensure sufficient glutamate uptake on a fast timescale, it is necessary to have high numbers of glutamate transporters in the vicinity of release sites to compensate for their slow transport kinetics. Using a combination of single molecule imaging and electrophysiological approaches, we now challenge this view by first demonstrating that GLT-1 transporters are not static but highly mobile at the surface of astrocytes, and that their surface diffusion is dependent upon both neuronal and glial cell activities. In the vicinity of glutamate synapses, GLT-1 dynamics are strongly reduced favoring their retention within this strategic location. Remarkably, glutamate uncaging at synaptic sites instantaneously increases GLT-1 diffusion, displacing the glutamate-bound transporter away from this compartment. Functionally, impairment of the transporter lateral diffusion through an antibody-based surface cross linking, both in vitro and in vivo, significantly slows the kinetics of excitatory postsynaptic currents. Taken together, these data reveal the unexpected and major role of the astrocytic surface GLT-1 fast dynamics in shaping glutamatergic synaptic transmission.Keywords:
Le glutamate est le principal neurotransmetteur excitateur du système nerveux central des vertébrés, et le codage de l’information cérébrale repose en partie sur des modulations de l’amplitude et de la fréquence des transmissions synaptiques glutamatergiques. De ce fait, la résolution spatiale et temporelle de ces transmissions nécessite un contrôle fin de la présence de glutamate dans la fente synaptique. Cette durée de vie du glutamate dans les synapses dépend directement de l’action de transporteurs spécifiques exprimés à la surface des astrocytes, en particulier les transporteurs de type GLT-1, qui retirent le neurotransmetteur et permettent ainsi de « nettoyer » la fente synaptique avant la survenue d’un nouvel épisode de neurotransmission.
Domaines
Neurosciences [q-bio.NC]| Origine | Version validée par le jury (STAR) |
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