Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins
Authors:Mehdi Kabani1
doi: 10.15698/mic2020.07.724
Volume 7, pp. 199 to 201, published 02/06/2020.
1 Institut de Biologie François Jacob, Molecular Imaging Research Center (MIRCen), Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Direction de la Recherche Fondamentale (DRF), Laboratoire des Maladies Neurodégénératives, Centre National de la Recherche Scientifique (CNRS), F-92265 Fontenay-aux-Roses.
Keywords:
yeast prions, prion-like proteins, extracellular vesicles, traffic
Corresponding Author(s):
Conflict of interest statement:
The author has no conflict of interest.
Please cite this article as:
Mehdi Kabani (2020). Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins. Microbial Cell 7(7): 199-201. doi: 10.15698/mic2020.07.724
© 2020 Kabani. This is an open-access article released under the terms of the Creative Com-mons Attribution (CC BY) license, which allows the unre-stricted use, distribution, and reproduction in any medi-um, provided the original author and source are acknowledged.
Abstract:
Infectious proteins or prions are non-native conformations of proteins that are the causative agents of devastating neurodegenerative diseases in humans and heritable traits in filamentous fungi and yeasts. Prion proteins form highly ordered self-perpetuating fibrillar aggregates that traffic vertically and horizontally from cell to cell. The spreading of these infectious entities relies on different mechanisms, among which the extracellular vesicles (EV)-mediated traffic. The prion form of the yeast Saccharomyces cerevisiae Sup35p translation terminator causes the [PSI+] nonsense suppression phenotype. This fascinating biological model helped us shape our understanding of the mechanisms of formation, propagation and elimination of infectious protein aggregates. We discovered that Sup35p is exported via EV, both in its soluble and aggregated infectious states. We recently reported that high amounts of Sup35p prion particles are exported to the yeast periplasm via periplasmic vesicles (PV) in glucose-starved cells. EV and PV are different in terms of size and protein content, and their export is inversely regulated by glucose availability in the growth medium. We believe these are important observations that should make us revise our current view on the way yeast prions propagate. Hence, I propose several hypotheses as to the significance of these observations for the transmission of yeast prions. I also discuss how yeast could be used as a powerful tractable biological model to investigate the molecular mechanisms of vesicle-mediated export of pathological protein aggregates implicated in neurodegenerative diseases.