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| Author(s): |
Laura Nogueira da Cruz
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2010-05-25 |
| Examining board members: |
Celia Regina da Silva Garcia;
Marcello Andre Barcinski;
Aline Maria da Silva;
Marta Maria Geraldes Teixeira;
Alexander Henning Ulrich
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| Advisor: | Celia Regina da Silva Garcia |
| Abstract | |
Malaria is a major health problem in developing countries Here we investigate the role of Ca2+ and purines in Plasmodium protease modulation. Using fluorescence resonance energy transfer (FRET) peptides, we verified protease activity elicited by Ca2+from endoplasmatic reticulum or acidic compartments and investigated the classes of affected proteases. Experiments in P. berghei and P. yoelii indicated a fundamental role for calcium in modulating proteolysis and points out key differences in proteolytic responses between Plasmodium species. We also investigated the effects of extracellular ATP, adenosine and GTP on triggering proteolysis. The data lead us to conclude that purinergic receptor is involved in the ability of the parasite to activate intracellular proteolysis by sensing external molecules. The third part of the thesis established a new murine knockout model to analyze Plasmodium-host signaling and suggest a possible interaction between InsP3R2 receptor and the PbRACK parasite protein. (AU) | |