Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR

Detalhes bibliográficos
Autor(a) principal: Roffe, Martin [UNIFESP]
Data de Publicação: 2010
Outros Autores: Beraldo, Flavio Henrique, Bester, Romina, Nunziante, Max, Bach, Christian, Mancini, Gabriel, Gilch, Sabine, Vorberg, Ina, Castilho, Beatriz Amaral de [UNIFESP], Martins, Vilma Regina, Maroso Hajj, Glaucia Noeli
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
dARK ID: ark:/48912/001300000ggbk
Texto Completo: http://dx.doi.org/10.1073/pnas.1000784107
http://repositorio.unifesp.br/handle/11600/32731
Resumo: Transmissible spongiform encephalopathies are fatal neurodegenerative diseases caused by the conversion of prion protein (PrPC) into an infectious isoform (PrPSc). How this event leads to pathology is not fully understood. Here we demonstrate that protein synthesis in neurons is enhanced via PrPC interaction with stress-inducible protein 1 (STI1). We also show that neuroprotection and neuritogenesis mediated by PrP(C)-STI1 engagement are dependent upon the increased protein synthesis mediated by PI3K-mTOR signaling. Strikingly, the translational stimulation mediated by PrP(C)-STI1 binding is corrupted in neuronal cell lines persistently infected with PrP(Sc), as well as in primary cultured hippocampal neurons acutely exposed to PrP(Sc). Consistent with this, high levels of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) phosphorylation were found in PrP(Sc)-infected cells and in neurons acutely exposed to PrP(Sc). These data indicate that modulation of protein synthesis is critical for PrP(C)-STI1 neurotrophic functions, and point to the impairment of this process during PrP(Sc) infection as a possible contributor to neurodegeneration.
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spelling Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTORprion scrapieneuritogenesisneuroprotectiontranslation initiationneurotrophic factorsTransmissible spongiform encephalopathies are fatal neurodegenerative diseases caused by the conversion of prion protein (PrPC) into an infectious isoform (PrPSc). How this event leads to pathology is not fully understood. Here we demonstrate that protein synthesis in neurons is enhanced via PrPC interaction with stress-inducible protein 1 (STI1). We also show that neuroprotection and neuritogenesis mediated by PrP(C)-STI1 engagement are dependent upon the increased protein synthesis mediated by PI3K-mTOR signaling. Strikingly, the translational stimulation mediated by PrP(C)-STI1 binding is corrupted in neuronal cell lines persistently infected with PrP(Sc), as well as in primary cultured hippocampal neurons acutely exposed to PrP(Sc). Consistent with this, high levels of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) phosphorylation were found in PrP(Sc)-infected cells and in neurons acutely exposed to PrP(Sc). These data indicate that modulation of protein synthesis is critical for PrP(C)-STI1 neurotrophic functions, and point to the impairment of this process during PrP(Sc) infection as a possible contributor to neurodegeneration.Ludwig Inst Canc Res, São Paulo Branch, BR-01323903 São Paulo, BrazilCtr Tratamento & Pesquisa AC Camargo, BR-01509010 São Paulo, BrazilDeutsch Zentrum Neurodegenerat Erkrankungen, D-53175 Bonn, GermanyUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, BrazilUniv Western Ontario, J Allyn Taylor Ctr Cell Biol, Mol Brain Res Grp, Robarts Res Inst, London, ON N6A 5K8, CanadaUniv Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5K8, CanadaTech Univ Munich, Inst Virol, D-80333 Munich, GermanyUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Programa Institutos Nacionais de Ciencia e TecnologiaConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP: 2008/00390FAPESP: 2002/12597-7FAPESP: 2003-13189-2FAPESP: 2008/53119-7Natl Acad SciencesLudwig Inst Canc ResCtr Tratamento & Pesquisa AC CamargoDeutsch Zentrum Neurodegenerat ErkrankungenUniversidade Federal de São Paulo (UNIFESP)Univ Western OntarioTech Univ MunichRoffe, Martin [UNIFESP]Beraldo, Flavio HenriqueBester, RominaNunziante, MaxBach, ChristianMancini, GabrielGilch, SabineVorberg, InaCastilho, Beatriz Amaral de [UNIFESP]Martins, Vilma ReginaMaroso Hajj, Glaucia Noeli2016-01-24T14:05:13Z2016-01-24T14:05:13Z2010-07-20info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13147-13152http://dx.doi.org/10.1073/pnas.1000784107Proceedings of the National Academy of Sciences of the United States of America. Washington: Natl Acad Sciences, v. 107, n. 29, p. 13147-13152, 2010.10.1073/pnas.10007841070027-8424http://repositorio.unifesp.br/handle/11600/32731WOS:000280144500079ark:/48912/001300000ggbkengProceedings of the National Academy of Sciences of the United States of Americainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2023-05-18T13:33:27Zoai:repositorio.unifesp.br/:11600/32731Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:17:12.583916Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR
title Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR
spellingShingle Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR
Roffe, Martin [UNIFESP]
prion scrapie
neuritogenesis
neuroprotection
translation initiation
neurotrophic factors
title_short Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR
title_full Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR
title_fullStr Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR
title_full_unstemmed Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR
title_sort Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR
author Roffe, Martin [UNIFESP]
author_facet Roffe, Martin [UNIFESP]
Beraldo, Flavio Henrique
Bester, Romina
Nunziante, Max
Bach, Christian
Mancini, Gabriel
Gilch, Sabine
Vorberg, Ina
Castilho, Beatriz Amaral de [UNIFESP]
Martins, Vilma Regina
Maroso Hajj, Glaucia Noeli
author_role author
author2 Beraldo, Flavio Henrique
Bester, Romina
Nunziante, Max
Bach, Christian
Mancini, Gabriel
Gilch, Sabine
Vorberg, Ina
Castilho, Beatriz Amaral de [UNIFESP]
Martins, Vilma Regina
Maroso Hajj, Glaucia Noeli
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ludwig Inst Canc Res
Ctr Tratamento & Pesquisa AC Camargo
Deutsch Zentrum Neurodegenerat Erkrankungen
Universidade Federal de São Paulo (UNIFESP)
Univ Western Ontario
Tech Univ Munich
dc.contributor.author.fl_str_mv Roffe, Martin [UNIFESP]
Beraldo, Flavio Henrique
Bester, Romina
Nunziante, Max
Bach, Christian
Mancini, Gabriel
Gilch, Sabine
Vorberg, Ina
Castilho, Beatriz Amaral de [UNIFESP]
Martins, Vilma Regina
Maroso Hajj, Glaucia Noeli
dc.subject.por.fl_str_mv prion scrapie
neuritogenesis
neuroprotection
translation initiation
neurotrophic factors
topic prion scrapie
neuritogenesis
neuroprotection
translation initiation
neurotrophic factors
description Transmissible spongiform encephalopathies are fatal neurodegenerative diseases caused by the conversion of prion protein (PrPC) into an infectious isoform (PrPSc). How this event leads to pathology is not fully understood. Here we demonstrate that protein synthesis in neurons is enhanced via PrPC interaction with stress-inducible protein 1 (STI1). We also show that neuroprotection and neuritogenesis mediated by PrP(C)-STI1 engagement are dependent upon the increased protein synthesis mediated by PI3K-mTOR signaling. Strikingly, the translational stimulation mediated by PrP(C)-STI1 binding is corrupted in neuronal cell lines persistently infected with PrP(Sc), as well as in primary cultured hippocampal neurons acutely exposed to PrP(Sc). Consistent with this, high levels of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) phosphorylation were found in PrP(Sc)-infected cells and in neurons acutely exposed to PrP(Sc). These data indicate that modulation of protein synthesis is critical for PrP(C)-STI1 neurotrophic functions, and point to the impairment of this process during PrP(Sc) infection as a possible contributor to neurodegeneration.
publishDate 2010
dc.date.none.fl_str_mv 2010-07-20
2016-01-24T14:05:13Z
2016-01-24T14:05:13Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1073/pnas.1000784107
Proceedings of the National Academy of Sciences of the United States of America. Washington: Natl Acad Sciences, v. 107, n. 29, p. 13147-13152, 2010.
10.1073/pnas.1000784107
0027-8424
http://repositorio.unifesp.br/handle/11600/32731
WOS:000280144500079
dc.identifier.dark.fl_str_mv ark:/48912/001300000ggbk
url http://dx.doi.org/10.1073/pnas.1000784107
http://repositorio.unifesp.br/handle/11600/32731
identifier_str_mv Proceedings of the National Academy of Sciences of the United States of America. Washington: Natl Acad Sciences, v. 107, n. 29, p. 13147-13152, 2010.
10.1073/pnas.1000784107
0027-8424
WOS:000280144500079
ark:/48912/001300000ggbk
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Proceedings of the National Academy of Sciences of the United States of America
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13147-13152
dc.publisher.none.fl_str_mv Natl Acad Sciences
publisher.none.fl_str_mv Natl Acad Sciences
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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