Liu Weifeng, Han Fang, Zhang Xiaobo
The Key Laboratory of Conservation Genetics and Reproductive Biology for Wild Animals of the Ministry of Education and College of Life Sciences, Zhejiang University, Hangzhou 310058, The People's Republic of China.
J Proteome Res. 2009 Mar;8(3):1198-206. doi: 10.1021/pr800840x.
Ran GTPases, one family of small G protein superfamily, have been widely demonstrated to be involved in the transport system between cytoplasm and the nucleus. However, the function of Ran GTPase in immunity remains unclear. In our study, it was found that the Ran GTPase (designated as PjRan) was up-regulated in virus-resistant shrimp, indicating that the PjRan might be implicated in the innate immune system against virus infection. On the basis of protein interactions, it was found that the PjRan interacted with myosin, a crucial protein in the process of phagocytosis to form a protein complex. The RNAi and mRNA assays showed that the PjRan could regulate shrimp hemocytic phagocytosis. Further data evidenced that the depletion of PjRan by RNAi caused a significant increase of virus copies, and the overexpression of PjRan resulted in a significant decrease of virus copies, suggesting that the PjRan participated in the antiviral immunity by regulating phagocytosis. Therefore, our study revealed a completely novel aspect of Ran GTPase in phagocytosis by the direct interaction with the cytoskeleton protein and presented a novel pathway concerning to antiviral immunity, which will help to better understand the molecular events in immune response against virus infection in invertebrates.
Ran GTP酶是小G蛋白超家族的一个成员,已被广泛证明参与细胞质与细胞核之间的运输系统。然而,Ran GTP酶在免疫中的功能仍不清楚。在我们的研究中,发现Ran GTP酶(命名为PjRan)在抗病毒对虾中上调,这表明PjRan可能参与了针对病毒感染的先天免疫系统。基于蛋白质相互作用,发现PjRan与肌球蛋白相互作用,肌球蛋白是吞噬作用过程中的一种关键蛋白质,二者形成一种蛋白质复合物。RNA干扰和mRNA分析表明,PjRan可以调节对虾血细胞的吞噬作用。进一步的数据证明,通过RNA干扰使PjRan缺失会导致病毒拷贝数显著增加,而PjRan的过表达则导致病毒拷贝数显著减少,这表明PjRan通过调节吞噬作用参与抗病毒免疫。因此,我们的研究通过与细胞骨架蛋白的直接相互作用揭示了Ran GTP酶在吞噬作用中一个全新的方面,并提出了一条与抗病毒免疫相关的新途径,这将有助于更好地理解无脊椎动物针对病毒感染的免疫反应中的分子事件。