EhRho1 regulates phagocytosis by modulating actin dynamics through EhFormin1 and EhProfilin1 in Entamoeba histolytica
EhRho1 regulates phagocytosis by modulating actin dynamics through EhFormin1 and EhProfilin1 in Entamoeba histolytica
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DOI：
10.1111/cmi.12851
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发表时间：
2018-09-01
影响因子：
3.4
通讯作者：
Bhattacharya, Alok
中科院分区：
文献类型：
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作者：
Bharadwaj, Ravi;Sharma, Shalini;Bhattacharya, Alok
原生寄生虫溶组织内阿米巴引起阿米巴病，这是发展中国家的一个主要公共卫生问题，也是发病率和死亡率的主要原因。阿米巴病的侵袭性感染主要影响肠上皮细胞衬里，但也可累及其他器官，如肝、肺或脑。吞噬作用是阿米巴营养的一种基本模式，通常与溶组织肠球菌的毒力行为有关。溶组织肠球菌具有高度动态和富含肌动蛋白的细胞骨架，被认为参与许多过程，如运动、伪足形成和发病机制。Rho GTP酶是肌动蛋白细胞骨架的关键调节因子，因此影响细胞的形状和运动。我们的研究主要集中在了解EhRho 1在溶组织艾美耳球虫的吞噬过程中的作用。EhRho 1与EhActin一起沿着富集在吞噬杯中，并保持与吞噬体膜的粘附。然而，没有直接结合的EhRho 1与G-或F-肌动蛋白，虽然结合观察到与肌动蛋白成核蛋白EhFormin 1和EhProfilin 1。在滋养体中过量表达显性失活突变体或通过反义RNA降低EhRho 1的表达，导致EhFormin 1和EhProfilin 1从吞噬杯中离域，从而导致吞噬过程受损和F-actin含量降低。总体结果表明，EhRho 1调节吞噬作用，通过调节肌动蛋白动力学，通过招聘EhFormin 1和EhProfilin 1在吞噬成核网站溶组织肠球菌。
The protist parasite Entamoeba histolytica causes amoebiasis, a major public health problem in developing countries and a major cause of morbidity and mortality. Invasive infection in amoebiasis mostly affects intestinal epithelial cell lining but can also involve other organs, such as liver, lungs, or brain. Phagocytosis is an essential mode of nutrition in amoeba and has often been associated with virulence behaviour of E.histolytica. E.histolytica possesses a highly dynamic and actin-rich cytoskeleton that is thought to be involved in many processes, such as motility, pseudopod formation, and pathogenesis. Rho GTPases are known to be key regulators of the actin cytoskeleton and consequently influence the shape and movement of cells. Our study is mainly focused to understand the role of EhRho1 in the phagocytosis process of E.histolytica. EhRho1 got enriched in the phagocytic cups along with EhActin and remains attached with phagosomal membrane. However, there was no direct binding of EhRho1 with G- or F-actin, though binding was observed with the actin nucleating proteins EhFormin1 and EhProfilin1. Overexpression of dominant negative mutant or lowering the expression by antisense RNA of EhRho1 in trophozoites caused delocalisation of EhFormin1 and EhProfilin1 from phagocytic cups, which results in impairment of phagocytic process and decrease in F-actin content. The overall results show that EhRho1 regulates phagocytosis by modulating actin dynamics through recruitment of EhFormin1 and EhProfilin1 at the phagocytosis nucleation site in E.histolytica.