Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles

ABSTRACT Prions are infectious protein particles that replicate by templating their aggregated state onto soluble protein of the same type. Originally identified as the causative agent of transmissible spongiform encephalopathies, prions in yeast (Saccharomyces cerevisiae) are epigenetic elements of...

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Autores principales:	Shu Liu, André Hossinger, Julia P. Hofmann, Philip Denner, Ina M. Vorberg
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/575fb5a91c9643c08b69cfb568e5e2da
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spelling	oai:doaj.org-article:575fb5a91c9643c08b69cfb568e5e2da2021-11-15T15:50:18ZHorizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles10.1128/mBio.00915-162150-7511https://doaj.org/article/575fb5a91c9643c08b69cfb568e5e2da2016-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00915-16https://doaj.org/toc/2150-7511ABSTRACT Prions are infectious protein particles that replicate by templating their aggregated state onto soluble protein of the same type. Originally identified as the causative agent of transmissible spongiform encephalopathies, prions in yeast (Saccharomyces cerevisiae) are epigenetic elements of inheritance that induce phenotypic changes of their host cells. The prototype yeast prion is the translation termination factor Sup35. Prions composed of Sup35 or its modular prion domain NM are heritable and are transmitted vertically to progeny or horizontally during mating. Interestingly, in mammalian cells, protein aggregates derived from yeast Sup35 NM behave as true infectious entities that employ dissemination strategies similar to those of mammalian prions. While transmission is most efficient when cells are in direct contact, we demonstrate here that cytosolic Sup35 NM prions are also released into the extracellular space in association with nanometer-sized membrane vesicles. Importantly, extracellular vesicles are biologically active and are taken up by recipient cells, where they induce self-sustained Sup35 NM protein aggregation. Thus, in mammalian cells, extracellular vesicles can serve as dissemination vehicles for protein-based epigenetic information transfer. IMPORTANCE Prions are proteinaceous infectious particles that propagate by templating their quaternary structure onto nascent proteins of the same kind. Prions in yeast act as heritable epigenetic elements that can alter the phenotype when transmitted to daughter cells or during mating. Prion activity is conferred by so-called prion domains often enriched in glutamine and asparagine residues. Interestingly, many mammalian proteins also contain domains with compositional similarity to yeast prion domains. We have recently provided a proof-of-principle demonstration that a yeast prion domain also retains its prion activity in mammalian cells. We demonstrate here that cytosolic prions composed of a yeast prion domain are also packaged into extracellular vesicles that transmit the prion phenotype to bystander cells. Thus, proteins with prion-like domains can behave as proteinaceous information molecules that exploit the cellular vesicle trafficking machinery for intercellular long-distance dissemination.Shu LiuAndré HossingerJulia P. HofmannPhilip DennerIna M. VorbergAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 4 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Shu Liu André Hossinger Julia P. Hofmann Philip Denner Ina M. Vorberg Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles
description	ABSTRACT Prions are infectious protein particles that replicate by templating their aggregated state onto soluble protein of the same type. Originally identified as the causative agent of transmissible spongiform encephalopathies, prions in yeast (Saccharomyces cerevisiae) are epigenetic elements of inheritance that induce phenotypic changes of their host cells. The prototype yeast prion is the translation termination factor Sup35. Prions composed of Sup35 or its modular prion domain NM are heritable and are transmitted vertically to progeny or horizontally during mating. Interestingly, in mammalian cells, protein aggregates derived from yeast Sup35 NM behave as true infectious entities that employ dissemination strategies similar to those of mammalian prions. While transmission is most efficient when cells are in direct contact, we demonstrate here that cytosolic Sup35 NM prions are also released into the extracellular space in association with nanometer-sized membrane vesicles. Importantly, extracellular vesicles are biologically active and are taken up by recipient cells, where they induce self-sustained Sup35 NM protein aggregation. Thus, in mammalian cells, extracellular vesicles can serve as dissemination vehicles for protein-based epigenetic information transfer. IMPORTANCE Prions are proteinaceous infectious particles that propagate by templating their quaternary structure onto nascent proteins of the same kind. Prions in yeast act as heritable epigenetic elements that can alter the phenotype when transmitted to daughter cells or during mating. Prion activity is conferred by so-called prion domains often enriched in glutamine and asparagine residues. Interestingly, many mammalian proteins also contain domains with compositional similarity to yeast prion domains. We have recently provided a proof-of-principle demonstration that a yeast prion domain also retains its prion activity in mammalian cells. We demonstrate here that cytosolic prions composed of a yeast prion domain are also packaged into extracellular vesicles that transmit the prion phenotype to bystander cells. Thus, proteins with prion-like domains can behave as proteinaceous information molecules that exploit the cellular vesicle trafficking machinery for intercellular long-distance dissemination.
format	article
author	Shu Liu André Hossinger Julia P. Hofmann Philip Denner Ina M. Vorberg
author_facet	Shu Liu André Hossinger Julia P. Hofmann Philip Denner Ina M. Vorberg
author_sort	Shu Liu
title	Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles
title_short	Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles
title_full	Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles
title_fullStr	Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles
title_full_unstemmed	Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles
title_sort	horizontal transmission of cytosolic sup35 prions by extracellular vesicles
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/575fb5a91c9643c08b69cfb568e5e2da
work_keys_str_mv	AT shuliu horizontaltransmissionofcytosolicsup35prionsbyextracellularvesicles AT andrehossinger horizontaltransmissionofcytosolicsup35prionsbyextracellularvesicles AT juliaphofmann horizontaltransmissionofcytosolicsup35prionsbyextracellularvesicles AT philipdenner horizontaltransmissionofcytosolicsup35prionsbyextracellularvesicles AT inamvorberg horizontaltransmissionofcytosolicsup35prionsbyextracellularvesicles
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Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles

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