Prions and exosomes: from PrPc trafficking to PrPsc propagation.
Exosomes are membrane vesicles released into the extracellular environment upon exocytic fusion of multivesicular endosomes with the cell surface. Exosome secretion can be used by cells to eject molecules targeted to intraluminal vesicles of multivesicular bodies, but particular cell types may exploit exosomes as intercellular communication devices for transfer of proteins and lipids among cells. The glycosylphosphatyidylinositol-linked prion protein (PrP) in both its normal (PrPc) and scrappie (PrPsc) conformation is associated with exosomes. Targeting of exosomes containing the normal cellular PrP could confer susceptibility of cells that do not express PrP to prion multiplication. Furthermore, exosomes bearing proteinase-K resistant PrPsc are infectious, suggesting a model in which exosomes secreted by infected cells could serve as vehicles for propagation of prions. Thus, cells may exploit the nature of endosome-derived exosomes to communicate with each other in normal and pathological situations, providing for a novel route of cell-to-cell communication and therefore of pathogen transmission. These findings open the possibility that methods to interfere with trafficking of such unconventional pathogens could be envisioned from insights on the mechanisms involved in exosome formation, secretion and targeting.
Porto-Carreiro
Isabel
I
Institut Curie, CNRS UMR 144, 75248 Paris, France. Isabel.Porto-Carreiro@curie.fr
Février
Benoît
B
Paquet
Sophie
S
Vilette
Didier
D
Raposo
Graça
G
D002450:Cell Communication; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D018621:PrPC Proteins / Q000378:metabolism; D018620:PrPSc Proteins / Q000096:biosynthesis; D017096:Prion Diseases / Q000209:etiology; D011328:Prions / Q000096:biosynthesis / Q000378:metabolism*; D021381:Protein Transport
D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions