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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.)

Starvation and rapamycin differentially regulate host cell lysosome exocytosis and invasion by Trypanosoma cruzi metacyclic forms

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Autor(es):
Martins, Rafael Miyazawa [1] ; Alves, Renan Melatto [1] ; Macedo, Silene [1] ; Yoshida, Nobuko [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 Sao Paulo - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: Cellular Microbiology; v. 13, n. 7, p. 943-954, JUL 2011.
Citações Web of Science: 37
Resumo

The molecular mechanisms of host cell invasion by T. cruzi metacyclic trypomastigotes (MT), the developmental forms that initiate infection in the mammalian host, are only partially understood. Here we aimed at further identifying the target cell components involved in signalling cascades leading to MT internalization, and demonstrate for the first time the participation of mammalian target of rapamycin (mTOR). Treatment of human epithelial HeLa cells with mTOR inhibitor rapamycin reduced lysosomal exocytosis and MT invasion. Downregulation of phosphatidylinositol 3-kinase and protein kinase C also impaired exocytosis and MT internalization. The recombinant protein based on gp82, the MT surface molecule that mediates cell adhesion/invasion, induced exocytosis in HeLa cells. Such an effect has not previously been attributed to any T. cruzi surface molecule. Rapamycin treatment diminished gp82 binding as well. Cell invasion assays under conditions that promoted lysosome exocytosis, such as 1 h incubation in starvation medium PBS(++), increased MT invasion, whereas pre-starvation of cells for 1-2 h had an opposite effect. In contrast to MT, invasion of tissue culture trypomastigotes (TCT) increased upon host cell pre-starvation or treatment with rapamycin, a novel finding that discloses quite distinctive features of the two infective forms in a key process for infection. (AU)

Processo FAPESP: 06/61450-0 - Estudos moleculares do Trypanosoma cruzi e de sua interação com células e fatores do hospedeiro in vitro e in vivo
Beneficiário:José Franco da Silveira Filho
Linha de fomento: Auxílio à Pesquisa - Temático