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RIOK-2 protein is essential for egg hatching in a common parasitic nematode.
International Journal for Parasitology ( IF 3.7 ) Pub Date : 2020-06-24 , DOI: 10.1016/j.ijpara.2020.05.004
Huan Zhou 1 , Taoxun Zhou 1 , Biying Zhang 1 , Weiqiang Lei 1 , Wang Yuan 1 , Jianan Shan 1 , Ying Zhang 1 , Nishith Gupta 2 , Min Hu 1
Affiliation  

The atypical protein kinase RIOK-2 is a non-ribosomal factor essential for ribosome maturation in yeast and human cells; however, little is known about its physiological role in pathogens. Our earlier work examined the expression profile of a RIOK-2 gene (Ss-riok-2) in Strongyloides stercoralis – a prevalent nematode parasite of dogs and humans. Herein, we demonstrate that Ss-RIOK-2 encodes a catalytically active kinase, distributed primarily in the cytoplasm of intestinal and hypodermal cells in transgenic larvae. Its expression oscillates as the free-living L1s develop into infective L3s. Overexpression of a catalytically impaired Ss-RIOK-2-D228A mutant delayed the development of transgenic larvae, while ectopic expression of another dominant negative isoform with a mutation in the ATP-binding site (K123A) abrogated the process of egg hatching, which could be rescued by co-expressing a wild-type Ss-RIOK-2 but not by its Ss-RIOK-1 ortholog. Collectively, our findings show a critical and specific role of Ss-RIOK-2 during the development of a pathogenic roundworm, which can be exploited to develop anti-infectives.



中文翻译:

RIOK-2 蛋白对于常见寄生线虫的卵孵化至关重要。

非典型蛋白激酶 RIOK-2 是一种非核糖体因子,对酵母和人类细胞中的核糖体成熟至关重要;然而,人们对其在病原体中的生理作用知之甚少。我们早期的工作检查了粪类圆线虫中RIOK-2 基因 ( Ss-riok-2 )的表达谱- 一种犬和人类普遍存在的线虫寄生虫。在本文中,我们表明,SS- RIOK-2编码具有催化活性的激酶,主要在肠和皮下细胞在转基因幼虫细胞质分布。它的表达随着自由生活的 L1s 发展成具有感染性的 L3s 而波动。过度表达催化受损的Ss-RIOK-2-D228A 突变体延迟了转基因幼虫的发育,而另一种在 ATP 结合位点 (K123A) 突变的显性负同种型的异位表达取消了卵孵化过程,这可以通过共同表达野生-type Ss- RIOK-2 但不是通过其Ss- RIOK-1 直系同源物。总的来说,我们的研究结果显示的关键和具体作用SS-致病性蛔虫,它可以用来开发抗感染药物的开发过程中RIOK-2。

更新日期:2020-07-28
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