Protein Synthesis Attenuation by Phosphorylation of eIF2 alpha Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms

Detalhes bibliográficos
Autor(a) principal: Tonelli, Renata R. [UNIFESP]
Data de Publicação: 2011
Outros Autores: Augusto, Leonardo da Silva [UNIFESP], Castilho, Beatriz A. [UNIFESP], Schenkman, Sergio [UNIFESP]
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.
id UFSP_0905f556a028346a94707563c9007458
oai_identifier_str oai:repositorio.unifesp.br/:11600/34226
network_acronym_str UFSP
network_name_str Repositório Institucional da UNIFESP
repository_id_str 3465
spelling 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
_version_ 1814268349046063104