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The GCaMP3 – A GFP-based calcium sensor for imaging calcium dynamics in the human malaria parasite Plasmodium falciparum

机译:GCaMP3 –一种基于GFP的钙传感器,可对人类疟疾寄生虫中的钙动力学成像[ce:italic>恶性疟原虫

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Graphical abstract Abstract Calcium (Ca 2+ ) signaling pathways are vital for all eukaryotic cells. It is well established that changes in Ca 2+ concentration can modulate several physiological processes such as muscle contraction, neurotransmitter secretion and metabolic regulation (Giacomello et al. (2007) [1], Rizzuto and Pozzan (2003) [2]). In the complex life cycle of Plasmodium falciparum , the causative agent of human malaria, Ca 2+ is involved in the processes of protein secretion, motility, cell invasion, cell progression and parasite egress from red blood cells (RBCs) (Koyama et al. (2009) [3]). The generation of P. falciparum expressing genetically encoded calcium indicators (GECIs) represents an innovation in the study of calcium signaling. This development will provide new insight on calcium homeostasis and signaling in P. falciparum . In addition, these novel transgenic parasites, PfGCaMP3, is a useful tool for screening and identifying new classes of compounds with anti-malarial activity. This represents a possibility of interfering with signaling pathways controlling parasite growth and development. Our new method differs from previous loading protocols (Garcia et al. (1996) [4]; Beraldo et al. (2007) [5]) since: ? It provides a novel method for imaging calcium fluctuations in the cytosol of P. falciparum , without signal interference from the host cell and invasive loading protocols. ? This technique could also be expanded for imaging calcium in different subcellular compartments. ? It will be helpful in the development of novel antimalarials capable of disrupting calcium homeostasis during the intraerythrocytic cycle of P. falciparum .
机译:图形摘要摘要钙(Ca 2+)信号通路对所有真核细胞都至关重要。众所周知,Ca 2+浓度的变化可以调节某些生理过程,例如肌肉收缩,神经递质分泌和代谢调节(Giacomello等(2007)[1],Rizzuto和Pozzan(2003)[2])。在人类疟疾的病原体恶性疟原虫的复杂生命周期中,Ca 2+参与蛋白质分泌,运动,细胞侵袭,细胞进程和从红细胞(RBC)寄生虫的过程(Koyama等。 (2009)[3]。表达遗传编码钙指示剂(GECI)的恶性疟原虫的产生代表了钙信号研究的一项创新。这一进展将为恶性疟原虫的钙稳态和信号传递提供新的见解。此外,这些新型转基因寄生虫PfGCaMP3是筛选和鉴定具有抗疟疾活性的新型化合物的有用工具。这代表可能干扰控制寄生虫生长和发育的信号传导途径。我们的新方法不同于以前的加载协议(Garcia等(1996)[4]; Beraldo等(2007)[5]),因为:它提供了一种新颖的方法来成像恶性疟原虫胞质中钙的波动,而没有来自宿主细胞和侵入性加载方案的信号干扰。 ?该技术还可扩展用于在不同的亚细胞区室中对钙成像。 ?这将有助于开发能够在恶性疟原虫的红细胞周期中破坏钙稳态的新型抗疟药。

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