Traffic membranaire des transporteurs du glutamate astrocytaires GLT-1
Language
en
Thèses de doctorat
Date
2014-06-06Speciality
Neurosciences
Doctoral school
École doctorale Sciences de la vie et de la santé (Bordeaux)Abstract
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 ...Read more >
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.Read less <
English Abstract
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 ...Read more >
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:Read less <
Keywords
Transporteurs du glutamate
Recapture du glutamate
Diffusion de surface
Imagerie de nanoparticules unique
Synapse tripartite
Interactions neurone-glie
English Keywords
Glutamate transporters
Glutamate uptake
Lateral diffusion
Single nanoparticle imaging
Tripartite synapse
Neuron-glia interactions
Origin
STAR importedCollections