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Cellular mechanisms responsible for cell-to-cell spreading of prions

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A Correction to this article was published on 11 June 2018

This article has been updated

Abstract

Prions are infectious agents that cause fatal neurodegenerative diseases. Current evidence indicates that they are essentially composed of an abnormally folded protein (PrPSc). These abnormal aggregated PrPSc species multiply in infected cells by recruiting and converting the host PrPC protein into new PrPSc. How prions move from cell to cell and progressively spread across the infected tissue is of crucial importance and may provide experimental opportunity to delay the progression of the disease. In infected cells, different mechanisms have been identified, including release of infectious extracellular vesicles and intercellular transfer of PrPSc-containing organelles through tunneling nanotubes. These findings should allow manipulation of the intracellular trafficking events targeting PrPSc in these particular subcellular compartments to experimentally address the relative contribution of these mechanisms to in vivo prion pathogenesis. In addition, such information may prompt further experimental strategies to decipher the causal roles of protein misfolding and aggregation in other human neurodegenerative diseases.

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Change history

  • 11 June 2018

    In the original publication, part of acknowledgement text was missing. The complete acknowledgement section should read as follows.

Abbreviations

BMDCs:

Bone-marrow-derived dendritic cells

ESCRT:

Endosomal sorting complex required for transport

EVs:

Extracellular vesicles

FDC:

Follicular dendritic cells

MVBs:

Multivesicular bodies

PMCA:

Protein misfolding cyclic amplification

TNTs:

Tunneling nanotubes

TSEs:

Transmissible spongiform encephalopathies

PrPC :

Normal form of the PrP protein in uninfected tissues or cells

PrPSc :

Misfolded form of PrP found in infected cells and tissues

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Acknowledgements

We thank Marie-Christine Miquel for comments and for carefully reading the manuscript.

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Authors and Affiliations

  1. UMR1225, INRA, ENVT, Ecole Nationale Vétérinaire, 23 Chemin des Capelles, Toulouse, France

    Didier Vilette & Olivier Andréoletti

  2. Neurosciences Paris Seine, UMR8246, Inserm U1130, IBPS, UPMC, Sorbonne Universités, 4 Place Jussieu, 75005, Paris, France

    Josquin Courte & Jean Michel Peyrin

  3. Insitut NeuroMyoGène, CNRS UMR5310, INSERM U1217, Faculté de Médecine Rockefeller, Université Claude Bernard Lyon I, 8 Avenue Rockefeller, 69373, Lyon Cedex 08, France

    Laurent Coudert, Laurent Schaeffer & Pascal Leblanc

  4. Laboratoire Physico Chimie Curie, UMR168, UPMC, IPGG, Sorbonne Universités, 6 Rue Jean Calvin, 75005, Paris, France

    Josquin Courte

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  1. Didier Vilette
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  2. Josquin Courte
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Correspondence to Didier Vilette, Jean Michel Peyrin or Pascal Leblanc.

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Vilette, D., Courte, J., Peyrin, J.M. et al. Cellular mechanisms responsible for cell-to-cell spreading of prions. Cell. Mol. Life Sci. 75, 2557–2574 (2018). https://doi.org/10.1007/s00018-018-2823-y

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  • DOI: https://doi.org/10.1007/s00018-018-2823-y

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