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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

A conserved domain of the gp85/trans-sialidase family activates host cell extracellular signal-regulated kinase and facilitates Tzypanosoma cruzi infection

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Autor(es):
Magdesian, Margaret H. ; Tonelli, Renata R. ; Fessel, Melissa R. ; Silveira, Mariana S. ; Schumacher, Robert I. ; Linden, Rafael ; Colli, Walter ; Alves, Maria Júlia M. [8]
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: Experimental Cell Research; v. 313, n. 1, p. 210-218, Jan. 2007.
Área do conhecimento: Ciências Biológicas - Bioquímica
Assunto(s):Protozoa   Trypanosoma cruzi   Fosforilação   Quinases de proteína quinase ativadas por mitógeno   Queratinas
Resumo

Chagas' disease is a chronic, debilitating and incapacitating illness, caused by the protozoan parasite Trypanosoma cruzi when infective trypomastigotes invade host cells. Although the mechanism of trypomastigotes interaction with mammalian cells has been intensively studied, a final and integrated picture of the signal transduction mechanisms involved still remains to be elucidated. Our group has previously shown that the conserved FLY domain (VTVXNVFLYNR), present in all members of the gp85/trans-sialidase glycoprotein family coating the surface of trypomastigotes, binds to cytokeratin 18 (CK18) on the surface of LLC-MK2 epithelial cells, and significantly increases parasite entry into mammalian cells. Now it is reported that FLY, present on the surface of trypomastigotes or on latex beads binds to CK18, promotes dephosphorylation and reorganization of CK18 and activation of the ERK1/2 signaling cascade culminating in an increase of approximately 9-fold in the number of parasites/cell. Inhibition of ERK1/2 phosphorylation completely blocks the adhesion of FLY to cells and blocks by 57% the host cell infection by T. cruzi. Taken together our results indicate that the conserved FLY domain is an important tool that trypomastigotes have evolved to specific exploit the host cell machinery and guarantee a successful infection. (AU)

Processo FAPESP: 04/03303-5 - Interação entre Trypanosoma cruzi e hospedeiro: ligantes, receptores e condicionantes do desenvolvimento intracelular
Beneficiário:Maria Julia Manso Alves
Modalidade de apoio: Auxílio à Pesquisa - Temático