graphic

Extracellular PrPsc (gold particles) is on exosome-like vesicles.

Raposo/NAS

When neurons are dying left and right, the mechanism of cell-to-cell spread of infectious prion proteins would not appear to be a problem in need of a solution.

But prions originally enter their hosts via the gut and must somehow reach the brain. Now, Benoit Fevrier, Graça Raposo (Institut Curie, Paris, France), and colleagues suggest that prions might travel at least partly via tiny vesicles called exosomes.

Exosomes form when late endosomes invaginate to form small, internal vesicles. The bag of vesicles, or multivesicular body (MVB), can fuse with the plasma membrane to disgorge these vesicles, named exosomes, which then travel to other cells to transmit messages. In the immune system, for example, exosomes transfer peptide-laden MHC proteins.

When the French group looked at the supernatant of PrPsc-infected epithelial and neuroglial cell cultures they found PrPsc. The released PrPsc was in a fraction consisting largely of vesicles that had the size and protein make-up of exosomes. PrPc was also seen in association with MVBs.

PrPsc may be able to transfer between cells that contact each other, but exosomes provide a plausible means for prions to traffic over longer distances. How this ties in with the normal function of PrPc is not clear. But if exosomes turn out to be an important mechanism of PrPsc migration, then blocking exosome secretion may slow down the spread of prion diseases. ▪

Reference:

Fevrier, B., et al. 2004. Proc. Natl. Acad. Sci. USA. 10.1073 pnas.0308413101.