School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, India.
PLoS Pathog. 2020 May 7;16(5):e1008214. doi: 10.1371/journal.ppat.1008214. eCollection 2020 May.
Calcium signaling plays a key role in many essential processes in almost all eukaryotic systems. It is believed that it may also be an important signaling system of the protist parasite Entamoeba histolytica. Motility, adhesion, cytolysis, and phagocytosis/trogocytosis are important steps in invasion and pathogenesis of E. histolytica, and Ca2+ signaling is thought to be associated with these processes leading to tissue invasion. There are a large number of Ca2+-binding proteins (CaBPs) in E. histolytica, and a number of these proteins appear to be associated with different steps in pathogenesis. The genome encodes 27 EF-hand-containing CaBPs in addition to a number of other Ca2+-binding domain/motif-containing proteins, which suggest intricate calcium signaling network in this parasite. Unlike other eukaryotes, a typical calmodulin-like protein has not been seen in E. histolytica. Though none of the CaBPs display sequence similarity with a typical calmodulin, extensive structural similarity has been seen in spite of lack of significant functional overlap with that of typical calmodulins. One of the unique features observed in E. histolytica is the identification of CaBPs (EhCaBP1, EhCaBP3) that have the ability to directly bind actin and modulate actin dynamics. Direct interaction of CaBPs with actin has not been seen in any other system. Pseudopod formation and phagocytosis are some of the processes that require actin dynamics, and some of the amoebic CaBPs (EhC2Pk, EhCaBP1, EhCaBP3, EhCaBP5) participate in this process. None of these E. histolytica CaBPs have any homolog in organisms other than different species of Entamoeba, suggesting a novel Ca2+ signaling pathway that has evolved in this genus.
钙信号在几乎所有真核生物系统的许多基本过程中都起着关键作用。据信，它也可能是原生动物寄生虫溶组织内阿米巴的重要信号系统。运动性、黏附性、细胞溶解和吞噬作用/转噬作用是溶组织内阿米巴侵袭和发病机制中的重要步骤，而 Ca2+信号被认为与导致组织侵袭的这些过程有关。溶组织内阿米巴中有大量的 Ca2+结合蛋白（CaBPs），其中一些蛋白似乎与发病机制的不同步骤有关。该基因组编码 27 种含有 EF 手的 CaBPs，以及许多其他含有 Ca2+结合域/基序的蛋白，这表明该寄生虫中存在复杂的钙信号网络。与其他真核生物不同，溶组织内阿米巴中没有看到典型的钙调蛋白样蛋白。尽管没有一种 CaBP 与典型的钙调蛋白具有序列相似性，但尽管与典型钙调蛋白的功能重叠不明显，但仍观察到广泛的结构相似性。溶组织内阿米巴中观察到的一个独特特征是鉴定出具有直接结合肌动蛋白并调节肌动蛋白动力学的 CaBPs（EhCaBP1、EhCaBP3）。在任何其他系统中都没有看到 CaBP 与肌动蛋白的直接相互作用。伪足形成和吞噬作用是一些需要肌动蛋白动力学的过程，而一些阿米巴 CaBP（EhC2Pk、EhCaBP1、EhCaBP3、EhCaBP5）参与了这一过程。在除不同种属的内阿米巴之外的生物体中，这些溶组织内阿米巴 CaBP 都没有任何同源物，这表明在该属中进化出了一种新的 Ca2+信号通路。
