| Grant number: | 13/50624-0 |
| Support Opportunities: | Research Projects - SPEC Program |
| Start date: | March 01, 2014 |
| End date: | February 29, 2020 |
| Field of knowledge: | Biological Sciences - Biochemistry - Biochemistry of Microorganisms |
| Principal Investigator: | Roberto Docampo |
| Grantee: | Roberto Docampo |
| Visiting researcher institution: | University of Georgia, Athens (UGA), United States |
| Host Institution: | Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil |
| Pesquisadores principais: | Silvia N J Moreno |
| Associated scholarship(s): | 17/25084-3 - Pyruvate metabolism function identification in Trypanosoma cruzi,
BP.PD 14/08995-4 - Calcium signaling in trypanosomatids, BP.PD 14/13148-9 - Calcium signaling in trypanosomatids, BP.PD |
Abstract
Regulation of Ca2+ homeostasis in trypanosomes differs significantly from that in mammalian cells. Trypanosomes possess an abundant acidic calcium store, the acidocalcisome, which is also rich in polyphosphate. Recent results from our group have indicated that acidocalcisomes possess an inositol 1,4,5-trisphosphate receptor (IP3R). These channels are usually located in the endoplasmic reticulum (ER) of mammalian cells. The IP3R is the primary cytosolic target responsible for the initiation of intracellular Ca2+ signaling in most eukaryotic cells. The release of Ca2+ via lP3Rs stimulates activities critical for life, but under some conditions IP3R-mediated Ca2+ signals are subverted to cause cell death, suggesting that this pathway is of potential therapeutic significance. The Ca2+ flow is facilitated by the close lP3R-mitochondrial calcium uniporter (MCU) connection. We hypothesize that Ca2+ signaling through the trypanosome IP3R has roles in growth in vitro and in vivo, and that the mitochondria of trypanosomes exert a regulatory role in Ca2+ signaling. The characterization of the pathways involving Ca2+ signaling in trypanosomes will lead to important insights into the biology of these parasites, the evolution of eukaryotic cells, and ultimately novel targets for anti-parasitic intervention. Our long-term goal is to uncover the Ca2+ signaling pathways in trypanosomes and with this information influence the design of therapeutic agents for parasite control. (AU)
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