A dominant negative form of inositol 1,4,5-trisphosphate receptor induces metacyclogenesis and increases mitochondrial density in Trypanosoma cruzi.
A dominant negative form of inositol 1,4,5-trisphosphate receptor induces metacyclogenesis and increases mitochondrial density in Trypanosoma cruzi.
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肌醇 1,4,5-三磷酸受体的显性失活形式可诱导克氏锥虫发生后生并增加线粒体密度。
DOI：
10.1016/j.bbrc.2015.09.053
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Mikoshiba K.
中科院分区：
文献类型：
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作者：
Hashimoto M;Nara T;Enomoto M;Kurebayashi N;Yoshida M;Sakurai T;Mita T;Mikoshiba K.
1，4，5-三磷酸肌醇受体（IP 3 R）是细胞内Ca 2+浓度的关键调节剂，它在各种外部刺激下从Ca 2+库中释放Ca 2+。IP 3R也作为一个信号中心，形成一个平台，与参与不同细胞信号传导的各种蛋白质相互作用。以前，我们已经确定了IP 3R同源的寄生原生生物，锥虫克氏锥虫（TcIP 3R）。寄生虫表达减少或增加水平的TcIP 3R显示缺陷的生长，转化和感染性。在本研究中，我们建立了表达显性负性形式的TcIP 3R的寄生菌株，命名为DN-TcIP 3R，以进一步研究TcIP 3R的生理作用。我们发现，表达DN-TcIP 3R的上鞭毛体的生长明显慢于TcIP 3R表达水平约为野生型水平的65%的寄生虫。DN-TcIP 3R在外鞭毛体中的表达即使在正常的生长培养基中也能诱导后循环发生。此外，这些外鞭毛体在透射电子显微镜下显示存在致密的线粒体。我们的研究结果证实，TcIP 3R是至关重要的epimastigote的增长，如前所述。他们还表明，IP 3R介导的信号传导的强烈抑制诱导元循环发生，并且线粒体完整性与该信号传导密切相关。
Inositol 1,4,5-trisphosphate receptor (IP3R) is a key regulator of intracellular Ca2+concentration that release Ca2+from Ca2+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.