Sup35p in Its Soluble and Prion States Is Packaged inside Extracellular Vesicles.

Most living cells in the three domains of life, Bacteria, Archaea, and Eukarya, secrete small membrane vesicles in the extracellular space. These extracellular vesicles (EV) were long viewed as "trash cans" by which cells disposed of unwanted macromolecules. EV gained renewed interest as their roles as vehicles for the cell-to-cell transfer of nucleic acids, signaling molecules, and pathogenic factors were recently uncovered. Of particular interest is their proposed role in the prion-like propagation of toxic protein aggregates in neurodegenerative diseases. Yeasts naturally harbor prion proteins that are excellent models to investigate the mechanisms of formation, propagation, and elimination of self-perpetuating protein aggregates. Here we show for the first time that a yeast prion is secreted within EV in its infectious aggregated state. A major implication of our work is the possibility of EV-mediated horizontal spread of fungal prions.