Referenced in: none

Automatically associated channels: Slo1

Title: A dominant negative form of inositol 1,4,5-trisphosphate receptor induces metacyclogenesis and increases mitochondrial density in Trypanosoma cruzi.

Authors: Muneaki Hashimoto, Takeshi Nara, Masahiro Enomoto, Nagomi Kurebayashi, Mitsutaka Yoshida, Takashi Sakurai, Toshihiro Mita, Katsuhiko Mikoshiba

Journal, date & volume: Biochem. Biophys. Res. Commun., 2015 Oct 23 , 466, 475-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26367178

Abstract
Inositol 1,4,5-trisphosphate receptor (IP3R) is a key regulator of intracellular Ca(2+) concentration that release Ca(2+) from Ca(2+) stores in response to various external stimuli. IP3R also works as a signal hub which form a platform for interacting with various proteins involved in diverse cell signaling. Previously, we have identified an IP3R homolog in the parasitic protist, Trypanosoma cruzi (TcIP3R). Parasites expressing reduced or increased levels of TcIP3R displayed defects in growth, transformation, and infectivity. In the present study, we established parasitic strains expressing a dominant negative form of TcIP3R, named DN-TcIP3R, to further investigate the physiological role(s) of TcIP3R. We found that the growth of epimastigotes expressing DN-TcIP3R was significantly slower than that of parasites with TcIP3R expression levels that were approximately 65% of wild-type levels. The expression of DN-TcIP3R in epimastigotes induced metacyclogenesis even in the normal growth medium. Furthermore, these epimastigotes showed the presence of dense mitochondria under a transmission electron microscope. Our findings confirm that TcIP3R is crucial for epimastigote growth, as previously reported. They also suggest that a strong inhibition of the IP3R-mediated signaling induces metacyclogenesis and that mitochondrial integrity is closely associated with this signaling.