School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
PLoS Pathog. 2019 May 16;15(5):e1007789. doi: 10.1371/journal.ppat.1007789. eCollection 2019 May.
The highly conserved proteins of the 14-3-3 family are universal adaptors known to regulate an enormous range of cellular processes in eukaryotes. However, their biological functions remain largely uncharacterized in pathogenic protists comprising of several 14-3-3 protein isoforms. In this study, we report the role of 14-3-3 in coordinating cytoskeletal dynamics during phagocytosis in a professional phagocytic protist Entamoeba histolytica, the etiological agent of human amebiasis. There are three isoforms of 14-3-3 protein in amoeba and here we have investigated Eh14-3-3 Protein 3 (EhP3). Live and fixed cell imaging studies revealed the presence of this protein throughout the parasite phagocytosis process, with high rate of accumulation at the phagocytic cups and closed phagosomes. Conditional suppression of EhP3 expression caused significant defects in phagocytosis accompanied by extensive diminution of F-actin at the site of cup formation. Downregulated cells also exhibited defective recruitment of an F-actin stabilizing protein, EhCoactosin at the phagocytic cups. In addition, mass spectrometry based analysis further revealed a large group of EhP3-associated proteins, many of these proteins are known to regulate cytoskeletal architecture in E histolytica. The dynamics of these proteins may also be controlled by EhP3. Taken together, our findings strongly suggest that EhP3 is a novel and a key regulatory element of actin dynamics and phagocytosis in E. histolytica.
14-3-3 家族的高度保守蛋白是普遍存在的衔接蛋白,已知它们在真核生物中调节着大量的细胞过程。然而,在包含多个 14-3-3 蛋白同工型的致病原生生物中,它们的生物学功能在很大程度上仍未被描述。在这项研究中,我们报告了 14-3-3 在协调原生动物中吞噬作用期间细胞骨架动力学的作用,原生动物是人类阿米巴病的病原体。在变形虫中有三种 14-3-3 蛋白同工型,我们在此研究了 Eh14-3-3 蛋白 3(EhP3)。活细胞和固定细胞成像研究表明,这种蛋白存在于寄生虫吞噬作用的整个过程中,在吞噬杯和闭合的吞噬体中积累速度很高。EhP3 表达的条件抑制导致吞噬作用严重缺陷,伴随着杯形成部位 F-肌动蛋白的大量减少。下调细胞也表现出在吞噬杯中 EhCoactosin 这种 F-肌动蛋白稳定蛋白的募集缺陷。此外,基于质谱的分析进一步揭示了一组大量与 EhP3 相关的蛋白,这些蛋白中的许多已知在 E histolytica 中调节细胞骨架结构。这些蛋白的动态也可能受 EhP3 控制。总之,我们的发现强烈表明,EhP3 是 E. histolytica 中肌动蛋白动力学和吞噬作用的一个新的关键调节元件。