Prion aggregates transfer through tunneling nanotubes in endocytic vesicles

Abstract : Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerativediseases caused by the misfolding of the cellular prion protein to an infectious form PrPSc.Theintercellular transfer of PrPScis a question of immediate interest as the cell-to-cell movement of theinfectious particle causes the inexorable propagation of disease. We have previously identified tunnelingnanotubes (TNTs) as one mechanism by which PrPSccan move between cells. Here we investigatefurther the details of this mechanism and show that PrPSctravels within TNTs in endolysosomal vesicles.Additionally we show that prion infection of CAD cells increases both the number of TNTs andintercellular transfer of membranous vesicles, thereby possibly playing an active role in its ownintercellular transfer via TNTs.