Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion

Detalhes bibliográficos
Autor(a) principal: Melo, Tatiana G.
Data de Publicação: 2020
Outros Autores: Coutinho, Eveline A., Pereira, Mirian Claudia S.
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/46370
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
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spelling Melo, Tatiana G.Coutinho, Eveline A.Pereira, Mirian Claudia S.2021-03-16T19:07:33Z2021-03-16T19:07:33Z2020MELO, Tatiane G.; COUTINHO, Eveline A.; PEREIRA, Mirian Claudia S. Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 115, e200143, 2020.0074-0276https://www.arca.fiocruz.br/handle/icict/4637010.1590/0074-027602001431678-8060porFundação Oswaldo Cruz. Instituto Oswaldo Cruz.Trypanosoma cruziProteoglicas de sulfato de heparanQuinasase de adesão focalCaminho de sinalizaçãoHeparan sulfate proteoglycansFocal adhesion kinaseTrypanosoma cruziSignaling pathwayHeparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.BACKGROUND Trypanosoma cruzi, the etiologic agent of Chagas disease, is capable of triggering different signaling pathways that modulate its internalisation in mammalian cells. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase protein, has been demonstrated as a mechanism of T. cruzi invasion in cardiomyocytes. Since the involved cell surface receptors are not yet known, we evaluated whether heparan sulfate proteoglycans (HSPG), a molecule involved in T. cruzi recognition and in the regulation of multiple signaling pathways, are able to trigger the FAK signaling pathway during T. cruzi invasion. METHODS To investigate the role of HSPG in the regulation of the FAK signaling pathway during trypomastigote entry, we performed heparan sulfate (HS) depletion from the cardiomyocyte surface by treatment with heparinase I or p-nitrophenyl- β-D-xylopyranoside (p-n-xyloside), which abolishes glycosaminoglycan (GAG) attachment to the proteoglycan core protein. Wild-type (CHO-k1) and GAG-deficient Chinese hamster ovary cells (CHO-745) were also used as an approach to evaluate the participation of the HSPG-FAK signaling pathway. FAK activation (FAK Tyr397) and spatial distribution were analysed by immunoblotting and indirect immunofluorescence, respectively. FINDINGS HS depletion from the cardiomyocyte surface inhibited FAK activation by T. cruzi. Cardiomyocyte treatment with heparinase I or p-n-xyloside resulted in 34% and 28% FAK phosphorylation level decreases, respectively. The experiments with the CHO cells corroborated the role of HSPG as a FAK activation mediator. T. cruzi infection did not stimulate FAK phosphorylation in CHO-745 cells, leading to a 36% reduction in parasite invasion. FAK inhibition due to the PF573228 treatment also impaired T. cruzi entry in CHO-k1 cells. MAIN CONCLUSION Jointly, our data demonstrate that HSPG is a key molecule in the FAK signaling pathway activation, regulating T. cruzi entry.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/46370/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALTatianaG_Melo_etal_IOC_2020.pdfTatianaG_Melo_etal_IOC_2020.pdfapplication/pdf3197789https://www.arca.fiocruz.br/bitstream/icict/46370/2/TatianaG_Melo_etal_IOC_2020.pdf6fae4f9d367ce9ba6db0fb449681262cMD52TEXTTatianaG_Melo_etal_IOC_2020.pdf.txtTatianaG_Melo_etal_IOC_2020.pdf.txtExtracted texttext/plain33794https://www.arca.fiocruz.br/bitstream/icict/46370/3/TatianaG_Melo_etal_IOC_2020.pdf.txt746f6881044a5b1ee57d54430816d1d1MD53icict/463702021-03-17 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dc.title.pt_BR.fl_str_mv Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion
title Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion
spellingShingle Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion
Melo, Tatiana G.
Trypanosoma cruzi
Proteoglicas de sulfato de heparan
Quinasase de adesão focal
Caminho de sinalização
Heparan sulfate proteoglycans
Focal adhesion kinase
Trypanosoma cruzi
Signaling pathway
title_short Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion
title_full Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion
title_fullStr Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion
title_full_unstemmed Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion
title_sort Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion
author Melo, Tatiana G.
author_facet Melo, Tatiana G.
Coutinho, Eveline A.
Pereira, Mirian Claudia S.
author_role author
author2 Coutinho, Eveline A.
Pereira, Mirian Claudia S.
author2_role author
author
dc.contributor.author.fl_str_mv Melo, Tatiana G.
Coutinho, Eveline A.
Pereira, Mirian Claudia S.
dc.subject.other.pt_BR.fl_str_mv Trypanosoma cruzi
Proteoglicas de sulfato de heparan
Quinasase de adesão focal
Caminho de sinalização
topic Trypanosoma cruzi
Proteoglicas de sulfato de heparan
Quinasase de adesão focal
Caminho de sinalização
Heparan sulfate proteoglycans
Focal adhesion kinase
Trypanosoma cruzi
Signaling pathway
dc.subject.en.pt_BR.fl_str_mv Heparan sulfate proteoglycans
Focal adhesion kinase
Trypanosoma cruzi
Signaling pathway
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
publishDate 2020
dc.date.issued.fl_str_mv 2020
dc.date.accessioned.fl_str_mv 2021-03-16T19:07:33Z
dc.date.available.fl_str_mv 2021-03-16T19:07:33Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv MELO, Tatiane G.; COUTINHO, Eveline A.; PEREIRA, Mirian Claudia S. Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 115, e200143, 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/46370
dc.identifier.issn.pt_BR.fl_str_mv 0074-0276
dc.identifier.doi.none.fl_str_mv 10.1590/0074-02760200143
dc.identifier.eissn.none.fl_str_mv 1678-8060
identifier_str_mv MELO, Tatiane G.; COUTINHO, Eveline A.; PEREIRA, Mirian Claudia S. Heparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 115, e200143, 2020.
0074-0276
10.1590/0074-02760200143
1678-8060
url https://www.arca.fiocruz.br/handle/icict/46370
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Fundação Oswaldo Cruz. Instituto Oswaldo Cruz.
publisher.none.fl_str_mv Fundação Oswaldo Cruz. Instituto Oswaldo Cruz.
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/46370/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/46370/2/TatianaG_Melo_etal_IOC_2020.pdf
https://www.arca.fiocruz.br/bitstream/icict/46370/3/TatianaG_Melo_etal_IOC_2020.pdf.txt
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