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Rémy Sadoul"Emerging role of exosomes in the central nervous system"

Abstract :


Exosomes are small extracellular vesicles, which stem from endosomes fusing with the plasma membrane, and can be recaptured by receiving cells.
They contain lipids, proteins and RNAs able to modify the physiology of receiving cells. Functioning of the brain relies on intercellular communication between neural cells. These communications can modulate the strength of responses at sparse groups of specific synapses, to modulate circuits underlying associations and memory. Expression of new genes must then follow to stabilize the long-term modifications of the synaptic response. Local changes of the physiology of synapses from one neuron driven by another, have so far been explained by classical signal transduction to modulate transcription, translation and post-translational modifications. In vitro evidence now demonstrate that exosomes are released by neurons in a way depending on synaptic activity; these exosomes can be retaken by other neurons suggesting a novel way for interneuronal communication. The efficacy of inter-neuronal transfer of biochemical information allowed by exosomes would be far superior to that of direct cell to-cell contacts or secreted soluble factors. Indeed, lipids, proteins and RNAs contained in exosomes secreted by emitting neurons could directly modify signal transduction and protein expression in receiving cells. Exosomes could thus represent an ideal mechanism for inter-neuronal transfer of information allowing anterograde and retrograde signalling across synapses necessary for plasticity. They might also allow pathological proteins to spread across the nervous system.

Selected publications

1. Fauré J., Lachenal G., Court M., Hirrlinger J., Chatellard-Causse C., Blot B., Grange J. Schoehn G., Goldberg Y., Boyer V., Kirchhoff F, Raposo G., Garin J., Sadoul R. 2006. Exosomes are released by cultured cortical neurones Mol Cell Neurosci. 31 (4):642-8.
2. Lachenal G, Pernet-Gallay K, Chivet M, Hemming FJ, Belly A, Bodon G, Blot B, Haase G, Goldberg Y, Sadoul R. 2011. Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity.Mol Cell Neurosci. 46(2):409

Scientific focus :

Neurodégénérescence et Plasticité

L’endocytose est un élément essentiel de la régulation de l'expression protéique à la surface cellulaire. Les protéines endocytées passent par les endosomes, dans lesquels elles sont triées vers d'autres organelles, la surface cellulaire, l'espace extracellulaire ou les lysosomes. Les liens entre les maladies neurodegeneratives et des mutations dans les effecteurs de la voie endosomale ainsi que des anomalies de ce système dans les neurones malades, posent la question du rapport entre ces anomalies et deux caractéristiques des pathologies neurodégénératives: les dysfonctions synaptiques et la mort neuronale.

David Perrais