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Efficient inhibition of infectious prions multiplication and release by targeting the exosomal pathway

Abstract : Exosomes are secreted membrane vesicles of endosomal origin present in biological fluids. Exosomes may serve as shuttles for amyloidogenic proteins, notably infectious prions, and may participate in their spreading in vivo. To explore the significance of the exosome pathway on prion infectivity and release, we investigated the role of the endosomal sorting complex required for transport (ESCRT) machinery and the need for ceramide, both involved in exosome biogenesis. Silencing of HRS-ESCRT-0 subunit drastically impairs the formation of cellular infectious prion due to an altered trafficking of cholesterol. Depletion of Tsg101-ESCRT-I subunit or impairment of the production of ceramide significantly strongly decreases infectious prion release. Together, our data reveal that ESCRT-dependent and -independent pathways can concomitantly regulate the exosomal secretion of infectious prion, showing that both pathways operate for the exosomal trafficking of a particular cargo. These data open up a new avenue to regulate prion release and propagation.
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https://hal.umontpellier.fr/hal-01842436
Contributeur : Alexandre Philips <>
Soumis le : mercredi 18 juillet 2018 - 12:03:50
Dernière modification le : mardi 21 juillet 2020 - 03:59:18

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Didier Vilette, Karine Laulagnier, Alvina Huor, Sandrine Alais, Sabrina Simoes, et al.. Efficient inhibition of infectious prions multiplication and release by targeting the exosomal pathway. Cellular and Molecular Life Sciences, Springer Verlag, 2015, 72 (22), pp.4409 - 4427. ⟨10.1007/s00018-015-1945-8⟩. ⟨hal-01842436⟩

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