Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo

Abstract Shadoo (Sho), a member of prion protein family, has been shown to prevent embryonic lethality in Prnp 0/0 mice and to be reduced in the brains of rodents with terminal prion diseases. Sho can also affect PrP structural dynamics and can increase the prion conversion into its misfolded isofor...

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Autores principales:	Anna Pepe, Rosario Avolio, Danilo Swann Matassa, Franca Esposito, Lucio Nitsch, Chiara Zurzolo, Simona Paladino, Daniela Sarnataro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a4316d3a77d4fc7be9465ba7d6814ea
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spelling	oai:doaj.org-article:1a4316d3a77d4fc7be9465ba7d6814ea2021-12-02T12:30:19ZRegulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo10.1038/s41598-017-03969-22045-2322https://doaj.org/article/1a4316d3a77d4fc7be9465ba7d6814ea2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03969-2https://doaj.org/toc/2045-2322Abstract Shadoo (Sho), a member of prion protein family, has been shown to prevent embryonic lethality in Prnp 0/0 mice and to be reduced in the brains of rodents with terminal prion diseases. Sho can also affect PrP structural dynamics and can increase the prion conversion into its misfolded isoform (PrPSc), which is amyloidogenic and strictly related to expression, intracellular localization and association of PrPC to lipid rafts. We reasoned that if Sho possesses a natural tendency to convert to amyloid-like forms in vitro, it should be able to exhibit “prion-like” properties, such as PK-resistance and aggregation state, also in live cells. We tested this hypothesis, by different approaches in neuronal cells, finding that Sho shows folding properties partially dependent on lipid rafts integrity whose alteration, as well as proteasomal block, regulated generation of intermediate Sho isoforms and exacerbated its misfolding. Moreover, a 18 kDa isoform of Sho, likely bearing the signal peptide, was targeted to mitochondria by interacting with the molecular chaperone TRAP1 which, in turn controlled Sho dual targeting to ER or mitochondria. Our studies contribute to understand the role of molecular chaperones and of PrP-related folding intermediates in “prion-like” conversion.Anna PepeRosario AvolioDanilo Swann MatassaFranca EspositoLucio NitschChiara ZurzoloSimona PaladinoDaniela SarnataroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Pepe Rosario Avolio Danilo Swann Matassa Franca Esposito Lucio Nitsch Chiara Zurzolo Simona Paladino Daniela Sarnataro Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo
description	Abstract Shadoo (Sho), a member of prion protein family, has been shown to prevent embryonic lethality in Prnp 0/0 mice and to be reduced in the brains of rodents with terminal prion diseases. Sho can also affect PrP structural dynamics and can increase the prion conversion into its misfolded isoform (PrPSc), which is amyloidogenic and strictly related to expression, intracellular localization and association of PrPC to lipid rafts. We reasoned that if Sho possesses a natural tendency to convert to amyloid-like forms in vitro, it should be able to exhibit “prion-like” properties, such as PK-resistance and aggregation state, also in live cells. We tested this hypothesis, by different approaches in neuronal cells, finding that Sho shows folding properties partially dependent on lipid rafts integrity whose alteration, as well as proteasomal block, regulated generation of intermediate Sho isoforms and exacerbated its misfolding. Moreover, a 18 kDa isoform of Sho, likely bearing the signal peptide, was targeted to mitochondria by interacting with the molecular chaperone TRAP1 which, in turn controlled Sho dual targeting to ER or mitochondria. Our studies contribute to understand the role of molecular chaperones and of PrP-related folding intermediates in “prion-like” conversion.
format	article
author	Anna Pepe Rosario Avolio Danilo Swann Matassa Franca Esposito Lucio Nitsch Chiara Zurzolo Simona Paladino Daniela Sarnataro
author_facet	Anna Pepe Rosario Avolio Danilo Swann Matassa Franca Esposito Lucio Nitsch Chiara Zurzolo Simona Paladino Daniela Sarnataro
author_sort	Anna Pepe
title	Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo
title_short	Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo
title_full	Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo
title_fullStr	Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo
title_full_unstemmed	Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo
title_sort	regulation of sub-compartmental targeting and folding properties of the prion-like protein shadoo
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1a4316d3a77d4fc7be9465ba7d6814ea
work_keys_str_mv	AT annapepe regulationofsubcompartmentaltargetingandfoldingpropertiesoftheprionlikeproteinshadoo AT rosarioavolio regulationofsubcompartmentaltargetingandfoldingpropertiesoftheprionlikeproteinshadoo AT daniloswannmatassa regulationofsubcompartmentaltargetingandfoldingpropertiesoftheprionlikeproteinshadoo AT francaesposito regulationofsubcompartmentaltargetingandfoldingpropertiesoftheprionlikeproteinshadoo AT lucionitsch regulationofsubcompartmentaltargetingandfoldingpropertiesoftheprionlikeproteinshadoo AT chiarazurzolo regulationofsubcompartmentaltargetingandfoldingpropertiesoftheprionlikeproteinshadoo AT simonapaladino regulationofsubcompartmentaltargetingandfoldingpropertiesoftheprionlikeproteinshadoo AT danielasarnataro regulationofsubcompartmentaltargetingandfoldingpropertiesoftheprionlikeproteinshadoo
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Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo

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