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- Title
Inositol 1,4,5-trisphosphate receptor determines intracellular Ca<sup>2+</sup> concentration in Trypanosoma cruzi throughout its life cycle.
- Authors
Hashimoto, Muneaki; Doi, Motomichi; Kurebayashi, Nagomi; Furukawa, Koji; Hirawake-Mogi, Hiroko; Ohmiya, Yoshihiro; Sakurai, Takashi; Mita, Toshihiro; Mikoshiba, Katsuhiko; Nara, Takeshi
- Abstract
Regulation of intracellular Ca2+ concentration ([Ca2+]i) is vital for eukaryotic organisms. Recently, we identified a Ca2+ channel (Tc IP3R) associated with intracellular Ca2+ stores in Trypanosoma cruzi, the parasitic protist that causes Chagas disease. In this study, we measured [Ca2+]i during the parasite life cycle and determined whether Tc IP3R is involved in the observed variations. Parasites expressing R- GECO1, a red fluorescent, genetically encoded Ca2+ indicator for optical imaging that fluoresces when bound to Ca2+, were produced. Using these R- GECO1-expressing parasites to measure [Ca2+]i, we found that the [Ca2+]i in epimastigotes was significantly higher than that in trypomastigotes and lower than that in amastigotes, and we observed a positive correlation between Tc IP 3 R mRNA expression and [Ca2+]i during the parasite life cycle both in vitro and in vivo. We also generated R- GECO1-expressing parasites with Tc IP3R expression levels that were approximately 65% of wild-type (wt) levels ( SKO parasites), and [Ca2+]i in the wt and SKO parasites was compared. The [Ca2+]i in SKO parasites was reduced to approximately 50-65% of that in wt parasites. These results show that Tc IP3R is the determinant of [Ca2+]i in T. cruzi. Since Ca2+ signaling is vital for these parasites, Tc IP3R is a promising drug target for Chagas disease.
- Subjects
INOSITOL; TRYPANOSOMA cruzi; MESSENGER RNA; GENE expression; CELLULAR signal transduction; IN vitro studies
- Publication
FEBS Open Bio, 2016, Vol 6, Issue 12, p1178
- ISSN
2211-5463
- Publication type
Article
- DOI
10.1002/2211-5463.12126