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PMID: 15210972 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cells release prions in association with exosomes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 26 ·2004-06-29 ·Pages 9683-8

Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H, Raposo G

Abstract

Prion diseases are infectious neurodegenerative disorders linked to the accumulation in the central nervous system of the abnormally folded prion protein (PrP) scrapie (PrPsc), which is thought to be the infectious agent. Once present, PrPsc catalyzes the conversion of naturally occurring cellular PrP (PrPc) to PrPsc. Prion infection is usually initiated in peripheral organs, but the mechanisms involved in infectious spread to the brain are unclear. We found that both PrPc and PrPsc were actively released into the extracellular environment by PrP-expressing cells before and after infection with sheep prions, respectively. Based on Western blot with specific markers, MS, and morphological analysis, our data revealed that PrPc and PrPsc in the medium are associated with exosomes, membranous vesicles that are secreted upon fusion of multivesicular endosomes with the plasma membrane. Furthermore, we found that exosomes bearing PrPsc are infectious. Our data suggest that exosomes may contribute to intercellular membrane exchange and the spread of prions throughout the organism.

MeSH Terms
Amyloid/deficiency,genetics,metabolism Animals Biological Assay Blotting, Western Brain/drug effects,metabolism Cell Extracts Cell Line Cell Membrane/metabolism Culture Media, Conditioned/chemistry,metabolism,pharmacology Endosomes/metabolism Exocytosis Extracellular Space/metabolism Gene Deletion Intracellular Membranes/metabolism Mass Spectrometry Mice Mice, Transgenic PrPSc Proteins/metabolism Prion Diseases/metabolism,transmission Prion Proteins Prions/metabolism Protein Precursors/deficiency,genetics,metabolism Secretory Vesicles/metabolism Sheep
Chemicals
Amyloid Cell Extracts Culture Media, Conditioned PrPSc Proteins Prion Proteins Prions Prnp protein, mouse Protein Precursors
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fevrier Benoit
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 144, Institut Curie, 75005 Paris, France.
Vilette Didier
Archer Fabienne
Loew Damarys
Faigle Wolfgang
Vidal Michel
Laude Hubert
Raposo Graça
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0308413101
Published
2004-06-29
Epub
2004-00-21
Pages
9683-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC470735
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0308413101 PMC Full Text View journal details
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