Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0027904 http://repositorio.unifesp.br/handle/11600/34226 |
Resumo: | Chagas' disease is a potentially life-threatening illness caused by the unicellular protozoan parasite Trypanosoma cruzi. It is transmitted to humans by triatomine bugs where T. cruzi multiplies and differentiates in the digestive tract. the differentiation of proliferative and non-infective epimastigotes into infective metacyclic trypomastigotes (metacyclogenesis) can be correlated to nutrient exhaustion in the gut of the insect vector. in vitro, metacyclic-trypomastigotes can be obtained when epimastigotes are submitted to nutritional stress suggesting that metacyclogenesis is triggered by nutrient starvation. the molecular mechanism underlying such event is not understood. Here, we investigated the role of one of the key signaling responses elicited by nutritional stress in all other eukaryotes, the inhibition of translation initiation by the phosphorylation of the eukaryotic initiation factor 2 alpha (eIF2 alpha), during the in vitro differentiation of T. cruzi. Monospecific antibodies that recognize the phosphorylated Tc-eIF2 alpha form were generated and used to demonstrate that parasites subjected to nutritional stress show increased levels of Tc-eIF2 alpha phosphorylation. This was accompanied by a drastic inhibition of global translation initiation, as determined by polysomal profiles. A strain of T. cruzi overexpressing a mutant Tc-eIF2 alpha, incapable of being phosphorylated, showed a block on translation initiation, indicating that such a nutritional stress in trypanosomatids induces the conserved translation inhibition response. in addition, Tc-eIF2 alpha phosphorylation is critical for parasite differentiation since the overexpression of the mutant eIF2 alpha in epimastigotes abolished metacyclogenesis. This work defines the role of eIF2 alpha phosphorylation as a key step in T. cruzi differentiation. |
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Repositório Institucional da UNIFESP |
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Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective FormsChagas' disease is a potentially life-threatening illness caused by the unicellular protozoan parasite Trypanosoma cruzi. It is transmitted to humans by triatomine bugs where T. cruzi multiplies and differentiates in the digestive tract. the differentiation of proliferative and non-infective epimastigotes into infective metacyclic trypomastigotes (metacyclogenesis) can be correlated to nutrient exhaustion in the gut of the insect vector. in vitro, metacyclic-trypomastigotes can be obtained when epimastigotes are submitted to nutritional stress suggesting that metacyclogenesis is triggered by nutrient starvation. the molecular mechanism underlying such event is not understood. Here, we investigated the role of one of the key signaling responses elicited by nutritional stress in all other eukaryotes, the inhibition of translation initiation by the phosphorylation of the eukaryotic initiation factor 2 alpha (eIF2 alpha), during the in vitro differentiation of T. cruzi. Monospecific antibodies that recognize the phosphorylated Tc-eIF2 alpha form were generated and used to demonstrate that parasites subjected to nutritional stress show increased levels of Tc-eIF2 alpha phosphorylation. This was accompanied by a drastic inhibition of global translation initiation, as determined by polysomal profiles. A strain of T. cruzi overexpressing a mutant Tc-eIF2 alpha, incapable of being phosphorylated, showed a block on translation initiation, indicating that such a nutritional stress in trypanosomatids induces the conserved translation inhibition response. in addition, Tc-eIF2 alpha phosphorylation is critical for parasite differentiation since the overexpression of the mutant eIF2 alpha in epimastigotes abolished metacyclogenesis. This work defines the role of eIF2 alpha phosphorylation as a key step in T. cruzi differentiation.Universidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Financiadora de Estudos e Projetos (FINEP)Public Library ScienceUniversidade Federal de São Paulo (UNIFESP)Tonelli, Renata R. [UNIFESP]Augusto, Leonardo da Silva [UNIFESP]Castilho, Beatriz A. [UNIFESP]Schenkman, Sergio [UNIFESP]2016-01-24T14:17:26Z2016-01-24T14:17:26Z2011-11-16info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10application/pdfhttp://dx.doi.org/10.1371/journal.pone.0027904Plos One. San Francisco: Public Library Science, v. 6, n. 11, 10 p., 2011.10.1371/journal.pone.0027904WOS000297555400138.pdf1932-6203http://repositorio.unifesp.br/handle/11600/34226WOS:000297555400138engPlos Oneinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-07-31T22:49:14Zoai:repositorio.unifesp.br/:11600/34226Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-07-31T22:49:14Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms |
title |
Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms |
spellingShingle |
Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms Tonelli, Renata R. [UNIFESP] |
title_short |
Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms |
title_full |
Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms |
title_fullStr |
Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms |
title_full_unstemmed |
Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms |
title_sort |
Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms |
author |
Tonelli, Renata R. [UNIFESP] |
author_facet |
Tonelli, Renata R. [UNIFESP] Augusto, Leonardo da Silva [UNIFESP] Castilho, Beatriz A. [UNIFESP] Schenkman, Sergio [UNIFESP] |
author_role |
author |
author2 |
Augusto, Leonardo da Silva [UNIFESP] Castilho, Beatriz A. [UNIFESP] Schenkman, Sergio [UNIFESP] |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Tonelli, Renata R. [UNIFESP] Augusto, Leonardo da Silva [UNIFESP] Castilho, Beatriz A. [UNIFESP] Schenkman, Sergio [UNIFESP] |
description |
Chagas' disease is a potentially life-threatening illness caused by the unicellular protozoan parasite Trypanosoma cruzi. It is transmitted to humans by triatomine bugs where T. cruzi multiplies and differentiates in the digestive tract. the differentiation of proliferative and non-infective epimastigotes into infective metacyclic trypomastigotes (metacyclogenesis) can be correlated to nutrient exhaustion in the gut of the insect vector. in vitro, metacyclic-trypomastigotes can be obtained when epimastigotes are submitted to nutritional stress suggesting that metacyclogenesis is triggered by nutrient starvation. the molecular mechanism underlying such event is not understood. Here, we investigated the role of one of the key signaling responses elicited by nutritional stress in all other eukaryotes, the inhibition of translation initiation by the phosphorylation of the eukaryotic initiation factor 2 alpha (eIF2 alpha), during the in vitro differentiation of T. cruzi. Monospecific antibodies that recognize the phosphorylated Tc-eIF2 alpha form were generated and used to demonstrate that parasites subjected to nutritional stress show increased levels of Tc-eIF2 alpha phosphorylation. This was accompanied by a drastic inhibition of global translation initiation, as determined by polysomal profiles. A strain of T. cruzi overexpressing a mutant Tc-eIF2 alpha, incapable of being phosphorylated, showed a block on translation initiation, indicating that such a nutritional stress in trypanosomatids induces the conserved translation inhibition response. in addition, Tc-eIF2 alpha phosphorylation is critical for parasite differentiation since the overexpression of the mutant eIF2 alpha in epimastigotes abolished metacyclogenesis. This work defines the role of eIF2 alpha phosphorylation as a key step in T. cruzi differentiation. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-11-16 2016-01-24T14:17:26Z 2016-01-24T14:17:26Z |
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/10.1371/journal.pone.0027904 Plos One. San Francisco: Public Library Science, v. 6, n. 11, 10 p., 2011. 10.1371/journal.pone.0027904 WOS000297555400138.pdf 1932-6203 http://repositorio.unifesp.br/handle/11600/34226 WOS:000297555400138 |
url |
http://dx.doi.org/10.1371/journal.pone.0027904 http://repositorio.unifesp.br/handle/11600/34226 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 6, n. 11, 10 p., 2011. 10.1371/journal.pone.0027904 WOS000297555400138.pdf 1932-6203 WOS:000297555400138 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Plos One |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
10 application/pdf |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
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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1814268349046063104 |