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

dc.creatorMelo, Tatiana G.
dc.creatorCoutinho, Eveline A.
dc.creatorPereira, Mirian Claudia S.
dc.date2021-03-16T19:07:33Z
dc.date2021-03-16T19:07:33Z
dc.date2020
dc.date.accessioned2023-09-26T22:12:45Z
dc.date.available2023-09-26T22:12:45Z
dc.identifierMELO, 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.identifier0074-0276
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/46370
dc.identifier10.1590/0074-02760200143
dc.identifier1678-8060
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8876317
dc.descriptionBACKGROUND 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.
dc.formatapplication/pdf
dc.languagepor
dc.publisherFundação Oswaldo Cruz. Instituto Oswaldo Cruz.
dc.rightsopen access
dc.subjectTrypanosoma cruzi
dc.subjectProteoglicas de sulfato de heparan
dc.subjectQuinasase de adesão focal
dc.subjectCaminho de sinalização
dc.subjectHeparan sulfate proteoglycans
dc.subjectFocal adhesion kinase
dc.subjectTrypanosoma cruzi
dc.subjectSignaling pathway
dc.titleHeparan sulfate proteoglycan triggers focal adhesion kinase signaling during Trypanosoma cruzi invasion
dc.typeArticle


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