De novo [PSI +] prion formation involves multiple pathways to form infectious oligomers

Abstract Prion and other neurodegenerative diseases are associated with misfolded protein assemblies called amyloid. Research has begun to uncover common mechanisms underlying transmission of amyloids, yet how amyloids form in vivo is still unclear. Here, we take advantage of the yeast prion, [PSI +...

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Autores principales:	Jaya Sharma, Brett T. Wisniewski, Emily Paulson, Joanna O. Obaoye, Stephen J. Merrill, Anita L. Manogaran
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5a38227647ac4f6fa2ac72c486fdc23c
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spelling	oai:doaj.org-article:5a38227647ac4f6fa2ac72c486fdc23c2021-12-02T11:52:21ZDe novo [PSI +] prion formation involves multiple pathways to form infectious oligomers10.1038/s41598-017-00135-62045-2322https://doaj.org/article/5a38227647ac4f6fa2ac72c486fdc23c2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00135-6https://doaj.org/toc/2045-2322Abstract Prion and other neurodegenerative diseases are associated with misfolded protein assemblies called amyloid. Research has begun to uncover common mechanisms underlying transmission of amyloids, yet how amyloids form in vivo is still unclear. Here, we take advantage of the yeast prion, [PSI +], to uncover the early steps of amyloid formation in vivo. [PSI +] is the prion form of the Sup35 protein. While [PSI +] formation is quite rare, the prion can be greatly induced by overexpression of the prion domain of the Sup35 protein. This de novo induction of [PSI +] shows the appearance of fluorescent cytoplasmic rings when the prion domain is fused with GFP. Our current work shows that de novo induction is more complex than previously thought. Using 4D live cell imaging, we observed that fluorescent structures are formed by four different pathways to yield [PSI +] cells. Biochemical analysis of de novo induced cultures indicates that newly formed SDS resistant oligomers change in size over time and lysates made from de novo induced cultures are able to convert [psi −] cells to [PSI +] cells. Taken together, our findings suggest that newly formed prion oligomers are infectious.Jaya SharmaBrett T. WisniewskiEmily PaulsonJoanna O. ObaoyeStephen J. MerrillAnita L. ManogaranNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jaya Sharma Brett T. Wisniewski Emily Paulson Joanna O. Obaoye Stephen J. Merrill Anita L. Manogaran De novo [PSI +] prion formation involves multiple pathways to form infectious oligomers
description	Abstract Prion and other neurodegenerative diseases are associated with misfolded protein assemblies called amyloid. Research has begun to uncover common mechanisms underlying transmission of amyloids, yet how amyloids form in vivo is still unclear. Here, we take advantage of the yeast prion, [PSI +], to uncover the early steps of amyloid formation in vivo. [PSI +] is the prion form of the Sup35 protein. While [PSI +] formation is quite rare, the prion can be greatly induced by overexpression of the prion domain of the Sup35 protein. This de novo induction of [PSI +] shows the appearance of fluorescent cytoplasmic rings when the prion domain is fused with GFP. Our current work shows that de novo induction is more complex than previously thought. Using 4D live cell imaging, we observed that fluorescent structures are formed by four different pathways to yield [PSI +] cells. Biochemical analysis of de novo induced cultures indicates that newly formed SDS resistant oligomers change in size over time and lysates made from de novo induced cultures are able to convert [psi −] cells to [PSI +] cells. Taken together, our findings suggest that newly formed prion oligomers are infectious.
format	article
author	Jaya Sharma Brett T. Wisniewski Emily Paulson Joanna O. Obaoye Stephen J. Merrill Anita L. Manogaran
author_facet	Jaya Sharma Brett T. Wisniewski Emily Paulson Joanna O. Obaoye Stephen J. Merrill Anita L. Manogaran
author_sort	Jaya Sharma
title	De novo [PSI +] prion formation involves multiple pathways to form infectious oligomers
title_short	De novo [PSI +] prion formation involves multiple pathways to form infectious oligomers
title_full	De novo [PSI +] prion formation involves multiple pathways to form infectious oligomers
title_fullStr	De novo [PSI +] prion formation involves multiple pathways to form infectious oligomers
title_full_unstemmed	De novo [PSI +] prion formation involves multiple pathways to form infectious oligomers
title_sort	de novo [psi +] prion formation involves multiple pathways to form infectious oligomers
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5a38227647ac4f6fa2ac72c486fdc23c
work_keys_str_mv	AT jayasharma denovopsiprionformationinvolvesmultiplepathwaystoforminfectiousoligomers AT bretttwisniewski denovopsiprionformationinvolvesmultiplepathwaystoforminfectiousoligomers AT emilypaulson denovopsiprionformationinvolvesmultiplepathwaystoforminfectiousoligomers AT joannaoobaoye denovopsiprionformationinvolvesmultiplepathwaystoforminfectiousoligomers AT stephenjmerrill denovopsiprionformationinvolvesmultiplepathwaystoforminfectiousoligomers AT anitalmanogaran denovopsiprionformationinvolvesmultiplepathwaystoforminfectiousoligomers
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De novo [PSI +] prion formation involves multiple pathways to form infectious oligomers

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