GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | por |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/41355 |
Resumo: | Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. |
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Malvezzi, Amaranta MunizAricó, MirellaSouza-Melo, NormandaSantos, Gregory Pedroso dosBittencourt-Cunha, PaulaHoletz, Fabíola BarbieriSchenkman, Sergio2020-05-21T22:18:09Z2020-05-21T22:18:09Z2020MALVEZZI, Amaranta Muniz et al. GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi. Frontiers in Cellular and Infection Microbiology. V.10, n.149, p. 1-15, 2020.2235-2988https://www.arca.fiocruz.br/handle/icict/4135510.3389/fcimb.2020.00149porFrontiers MediaTrypanosoma cruziCRISPREukaryotic Initiation Factor-2PhosphorylationCytoplasmic GranulesProtein KinasesClustered Regularly Interspaced Short Palindromic RepeatsFactor 2 Eucariótico de IniciaciónFosforilaciónGránulos CitoplasmáticosProteínas QuinasasRepeticiones Palindrómicas Cortas Agrupadas y Regularmente EspaciadasFator de Iniciação 2 em EucariotosFosforilaçãoGrânulos CitoplasmáticoProteínas QuinasesRepetições Palindrômicas Curtas Agrupadas e Regularmente EspaçadasGCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruziinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.The integrated stress response in eukaryotic cells is an orchestrated pathway that leads to eukaryotic Initiation Factor 2 alpha subunit (eIF2α) phosphorylation at ser51 and ultimately activates pathways to mitigate cellular damages. Three putative kinases (Tck1, Tck2, and Tck3) are found in the Trypanosoma cruzi genome, the flagellated parasite that causes Chagas disease. These kinases present similarities to other eukaryotic eIF2α kinases, exhibiting a typical insertion loop in the kinase domain of the protein. We found that this insertion loop is conserved among kinase 1 of several T. cruzi strains but differs among various Kinetoplastidae species, suggesting unique roles. Kinase 1 is orthologous of GCN2 of several eukaryotes, which have been implicated in the eIF2α ser51 phosphorylation in situations that mainly affects the nutrients levels. Therefore, we further investigated the responses to nutritional stress of T. cruzi devoid of TcK1 generated by CRISPR/Cas9 gene replacement. In nutrient-rich conditions, replicative T. cruzi epimastigotes depleted of TcK1 proliferate as wild type cells but showed increased levels of polysomes relative to monosomes. Upon nutritional deprivation, the polysomes decreased more than in TcK1 depleted line. However, eIF2α is still phosphorylated in TcK1 depleted line, as in wild type parasites. eIF2α phosphorylation increased at longer incubations times, but KO parasites showed less accumulation of ribonucleoprotein granules containing ATP-dependent RNA helicase involved in mRNA turnover (DHH1) and Poly-A binding protein (PABP1). Additionally, the formation of metacyclic-trypomastigotes is increased in the absence of Tck1 compared to controls. These metacyclics, as well as tissue culture trypomastigotes derived from the TcK1 knockout line, were less infective to mammalian host cells, although replicated faster inside mammalian cells. These results indicate that GCN2-like kinase in T. cruzi affects stress granule formation, independently of eIF2α phosphorylation upon nutrient deprivation. It also modulates the fate of the parasites during differentiation, invasion, and intracellular proliferation.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83084https://www.arca.fiocruz.br/bitstream/icict/41355/1/license.txt783568c2893d2e25a99990b126be1772MD51ORIGINALfcimb-10-0014.pdffcimb-10-0014.pdfapplication/pdf2172447https://www.arca.fiocruz.br/bitstream/icict/41355/2/fcimb-10-0014.pdfd4cca5ff5fed06e12b73331195384b7cMD52TEXTfcimb-10-0014.pdf.txtfcimb-10-0014.pdf.txtExtracted texttext/plain74092https://www.arca.fiocruz.br/bitstream/icict/41355/3/fcimb-10-0014.pdf.txt4addd93a7ac5d744695177e501cf37d5MD53icict/413552022-12-12 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| dc.title.pt_BR.fl_str_mv |
GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi |
| title |
GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi |
| spellingShingle |
GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi Malvezzi, Amaranta Muniz Trypanosoma cruzi CRISPR Eukaryotic Initiation Factor-2 Phosphorylation Cytoplasmic Granules Protein Kinases Clustered Regularly Interspaced Short Palindromic Repeats Factor 2 Eucariótico de Iniciación Fosforilación Gránulos Citoplasmáticos Proteínas Quinasas Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas Fator de Iniciação 2 em Eucariotos Fosforilação Grânulos Citoplasmático Proteínas Quinases Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas |
| title_short |
GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi |
| title_full |
GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi |
| title_fullStr |
GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi |
| title_full_unstemmed |
GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi |
| title_sort |
GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi |
| author |
Malvezzi, Amaranta Muniz |
| author_facet |
Malvezzi, Amaranta Muniz Aricó, Mirella Souza-Melo, Normanda Santos, Gregory Pedroso dos Bittencourt-Cunha, Paula Holetz, Fabíola Barbieri Schenkman, Sergio |
| author_role |
author |
| author2 |
Aricó, Mirella Souza-Melo, Normanda Santos, Gregory Pedroso dos Bittencourt-Cunha, Paula Holetz, Fabíola Barbieri Schenkman, Sergio |
| author2_role |
author author author author author author |
| dc.contributor.author.fl_str_mv |
Malvezzi, Amaranta Muniz Aricó, Mirella Souza-Melo, Normanda Santos, Gregory Pedroso dos Bittencourt-Cunha, Paula Holetz, Fabíola Barbieri Schenkman, Sergio |
| dc.subject.other.pt_BR.fl_str_mv |
Trypanosoma cruzi CRISPR |
| topic |
Trypanosoma cruzi CRISPR Eukaryotic Initiation Factor-2 Phosphorylation Cytoplasmic Granules Protein Kinases Clustered Regularly Interspaced Short Palindromic Repeats Factor 2 Eucariótico de Iniciación Fosforilación Gránulos Citoplasmáticos Proteínas Quinasas Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas Fator de Iniciação 2 em Eucariotos Fosforilação Grânulos Citoplasmático Proteínas Quinases Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas |
| dc.subject.en.pt_BR.fl_str_mv |
Eukaryotic Initiation Factor-2 Phosphorylation Cytoplasmic Granules Protein Kinases Clustered Regularly Interspaced Short Palindromic Repeats |
| dc.subject.es.pt_BR.fl_str_mv |
Factor 2 Eucariótico de Iniciación Fosforilación Gránulos Citoplasmáticos Proteínas Quinasas Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas |
| dc.subject.decs.pt_BR.fl_str_mv |
Fator de Iniciação 2 em Eucariotos Fosforilação Grânulos Citoplasmático Proteínas Quinases Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas |
| description |
Universidade Federal de São Paulo. Escola Paulista de Medicina. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil. |
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2020 |
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2020-05-21T22:18:09Z |
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2020-05-21T22:18:09Z |
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2020 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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MALVEZZI, Amaranta Muniz et al. GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi. Frontiers in Cellular and Infection Microbiology. V.10, n.149, p. 1-15, 2020. |
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https://www.arca.fiocruz.br/handle/icict/41355 |
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2235-2988 |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fcimb.2020.00149 |
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MALVEZZI, Amaranta Muniz et al. GCN2-Like Kinase modulates stress granule formation during nutritional stress in Trypanosoma cruzi. Frontiers in Cellular and Infection Microbiology. V.10, n.149, p. 1-15, 2020. 2235-2988 10.3389/fcimb.2020.00149 |
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Frontiers Media |
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