Prion protein interaction with stress-inducible protein 1 enhances neuronal protein synthesis via mTOR
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , , , , , |
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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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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1818602461065117696 |