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Abstract
Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases caused by the misfolding of the cellular prion protein to an infectious form PrPSc. The intercellular transfer of PrPSc is a question of immediate interest as the cell-to-cell movement of the infectious particle causes the inexorable propagation of disease. We have previously identified tunneling nanotubes (TNTs) as one mechanism by which PrPSc can move between cells. Here we investigate further the details of this mechanism and show that PrPSc travels within TNTs in endolysosomal vesicles. Additionally we show that prion infection of CAD cells increases both the number of TNTs and intercellular transfer of membranous vesicles, thereby possibly playing an active role in its own intercellular transfer via TNTs.
DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
No potential conflicts of interest were disclosed.
Acknowledgments
The authors thank all lab members for discussion.
Funding
SZ is supported by a PhD fellowship from the Chinese Scholarship Council. GSV is supported by fellowships from the Fondation Recherche Médicale and the Bourse Pasteur-Roux, Institut Pasteur. This work is supported by research grants from the European Commission FP7 PRIORITY contract number 222887, the MI CARNOT ICSA/PMI, grants from the region Ile-de-France (IDF DIM-MALINF 2013), Agence Nationale de la Recherche (ANR-14-JPCD-0002–01) and Equipe FRM (Fondation Recherche Medicale) 2014 (DEQ20140329557) to CZ.