Efficient inhibition of infectious prions multiplication and release by targeting the exosomal pathway - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Cellular and Molecular Life Sciences Year : 2015

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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Dates and versions

hal-01842436 , version 1 (18-07-2018)

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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, 2015, 72 (22), pp.4409 - 4427. ⟨10.1007/s00018-015-1945-8⟩. ⟨hal-01842436⟩
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