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

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 u...

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Autores principales: Sharma, Jaya, Wisniewski, Brett T., Paulson, Emily, Obaoye, Joanna O., Merrill, Stephen J., Manogaran, Anita L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427932/
https://www.ncbi.nlm.nih.gov/pubmed/28250435
http://dx.doi.org/10.1038/s41598-017-00135-6
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author Sharma, Jaya
Wisniewski, Brett T.
Paulson, Emily
Obaoye, Joanna O.
Merrill, Stephen J.
Manogaran, Anita L.
author_facet Sharma, Jaya
Wisniewski, Brett T.
Paulson, Emily
Obaoye, Joanna O.
Merrill, Stephen J.
Manogaran, Anita L.
author_sort Sharma, Jaya
collection PubMed
description 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.
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spelling pubmed-54279322017-05-12 De novo [PSI(+)] prion formation involves multiple pathways to form infectious oligomers Sharma, Jaya Wisniewski, Brett T. Paulson, Emily Obaoye, Joanna O. Merrill, Stephen J. Manogaran, Anita L. Sci Rep Article 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. Nature Publishing Group UK 2017-03-06 /pmc/articles/PMC5427932/ /pubmed/28250435 http://dx.doi.org/10.1038/s41598-017-00135-6 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Sharma, Jaya
Wisniewski, Brett T.
Paulson, Emily
Obaoye, Joanna O.
Merrill, Stephen J.
Manogaran, Anita L.
De novo [PSI(+)] prion formation involves multiple pathways to form infectious oligomers
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427932/
https://www.ncbi.nlm.nih.gov/pubmed/28250435
http://dx.doi.org/10.1038/s41598-017-00135-6
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