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Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins

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 vertic...

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Autor principal: Kabani, Mehdi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shared Science Publishers OG 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328675/
https://www.ncbi.nlm.nih.gov/pubmed/32656259
http://dx.doi.org/10.15698/mic2020.07.724
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author Kabani, Mehdi
author_facet Kabani, Mehdi
author_sort Kabani, Mehdi
collection PubMed
description 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.
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spelling pubmed-73286752020-07-09 Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins Kabani, Mehdi Microb Cell Microreview 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. Shared Science Publishers OG 2020-06-02 /pmc/articles/PMC7328675/ /pubmed/32656259 http://dx.doi.org/10.15698/mic2020.07.724 Text en Copyright: © 2020 Kabani https://creativecommons.org/licenses/by/4.0/ This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
spellingShingle Microreview
Kabani, Mehdi
Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins
title Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins
title_full Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins
title_fullStr Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins
title_full_unstemmed Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins
title_short Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins
title_sort hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins
topic Microreview
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328675/
https://www.ncbi.nlm.nih.gov/pubmed/32656259
http://dx.doi.org/10.15698/mic2020.07.724
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