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Role of exosomes in intercellular trafficking of APP

Objectifs

Study using biochemical and microscopical techniques, the way the amyloid precursor protein and proteolytic fragments, including the Abeta peptide, are transferred between brain neurons in culture.

Résumé

Amyloid beta peptide, the main component of senile plaques of Alzheimer’s disease brains, is produced by sequential cleavage of Amyloid Precursor Protein (APP) and of its C-terminal fragments (CTFs). An unanswered question is how amyoïdogenic peptides spread throughout the brain during the course of the disease. The project deals with the role of small lipid vesicles called exosomes, secreted in the extracellular milieu by cortical neurons carry APP and CTFs between neurons. The student will characterize the subset of exosomes carrying APP, which specifically binds to dendrites of neurons. For this he(she) will use rodent cortical cultures, biochemical approaches, and confocal microscopy. The student will also study how exosomes from Alix ko mice differ from those of wt mice in order to explain our recent finding that the lack of Alix protects against the accumulation of Abeta containing plaques.

Méthodes

Neuronal cell culture. Analytical centrifugation. Fluorescence microscopy. Electron microscopy.

Références

  • Faure, 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. Molecular and cellular neurosciences 31, 642-648.

  • Lachenal, G., Pernet-Gallay, K., Chivet, M., Hemming, F.J., Belly, A., Bodon, G., Blot, B., Haase, G., Goldberg, Y., and Sadoul, R. (2011). Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Molecular and cellular neurosciences 46, 409-418.

  • Chivet, M., Javalet, C., Laulagnier, K., Blot, B., Hemming , F.J., Sadoul R. (2014) Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons. J Extracell Vesicles. 2014 Nov 13;3:24722

Contacts

Rémy Sadoul, PR1 UGA
Email : remy.sadoul@univ-grenoble-alpes.fr


Mise à jour le 29 mai 2017

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