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Exosomes neuronaux: sécrétion de protéines membranaires impliquées dans les processus physiologiques et pathologiques du système nerveux.

Abstract : Exosomes are microvesicles secreted by many cells upon fusion of multivesicular endosomes with plasma membrane. They allow the intercellular transfer of proteins, lipids and RNA. They are especially well described in the immune system, where they induce an anti-tumoral response by the exchange of MHC molecules between dendritic cells. We are interested in the role exosomes could play in the nervous system. We first described that primary neurons do secrete exosomes as they differenciate. Then we showed that mature neurones also secrete exosomes. Neuronal exosomes contain sub-units of glutamate receptors (GluR1 and 2), and the endogenous prion protein (PrPc). We also showed that the C-terminal part of the tetanus toxin can be released in association with neuronal exosomes. Finally, we demonstrated that neuronal exosomal release is regulated by synaptic glutamatergic activity, and by a Ca2+ influx. Using a cell line as a model, we studied the exosomal release of APP (amyloid precursor protein) and its derivates according to mutations found in familial forms of Alzheimer disease. We showed that exosomes contain the amyloidogenic fragment of APP C99. It has also been shown that exosomes from a cell line overexpressing APP contain a fraction of the secreted Aβ, involved in Alzheimer disease. Neuronal exosomes could play a crucial role in the normal physiology of synapses, by allowing the exchange of neurotransmitter receptors between neurons. They could also propagate pathogenic proteins involved in neurodegenerative disorders such as Alzheimer and Creutzfeldt-Jacob diseases.
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https://tel.archives-ouvertes.fr/tel-00481716
Contributor : Gaelle Moisand Lachenal <>
Submitted on : Friday, May 7, 2010 - 12:48:43 PM
Last modification on : Friday, November 6, 2020 - 4:07:24 AM
Long-term archiving on: : Thursday, September 16, 2010 - 1:49:29 PM

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  • HAL Id : tel-00481716, version 1

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UJF | U836 | UGA

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Gaelle Moisand Lachenal. Exosomes neuronaux: sécrétion de protéines membranaires impliquées dans les processus physiologiques et pathologiques du système nerveux.. Biologie cellulaire. Université Joseph-Fourier - Grenoble I, 2009. Français. ⟨tel-00481716⟩

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