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Starvation and rapamycin differentially regulate host cell lysosome exocytosis and invasion by Trypanosomacruzi metacyclic forms.
MedLine Citation:
PMID:  21501360     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 signaling 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 exocoytosis 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 prestarvation of cells for 1-2 h had an opposite effect. In contrast to MT, invasion of tissue culture trypomastigotes (TCT) increased upon host cell prestarvation or treatment with rapamycin, a novel finding that discloses quite distinctive features of the two infective forms in a key process for infection.
Authors:
Rafael Miyazawa Martins; Renan Melatto Alves; Silene Macedo; Nobuko Yoshida
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-15
Journal Detail:
Title:  Cellular microbiology     Volume:  -     ISSN:  1462-5822     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-4-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 Blackwell Publishing Ltd.
Affiliation:
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, R. Botucatu, 862, 6o andar, 04023-062, São Paulo, Brasil.
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