State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China.
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People's Republic of China; Department of Molecular Parasitology, Faculty of Life Sciences, Humboldt University, Berlin, Germany.
Int J Parasitol. 2020 Jul;50(8):595-602. doi: 10.1016/j.ijpara.2020.05.004. Epub 2020 Jun 24.
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.
非典型蛋白激酶 RIOK-2 是一种非核糖体因子，对于酵母和人类细胞中的核糖体成熟是必需的；然而，其在病原体中的生理作用知之甚少。我们之前的工作研究了 Strongyloides stercoralis（一种普遍存在的犬和人类寄生线虫）中 RIOK-2 基因（Ss-riok-2）的表达谱。在此，我们证明 Ss-RIOK-2 编码一种具有催化活性的激酶，主要分布在转染幼虫的肠细胞和皮下细胞的细胞质中。其表达随着自由生活的 L1 发育成感染性的 L3 而波动。过表达催化失活的 Ss-RIOK-2-D228A 突变体延迟了转基因幼虫的发育，而在 ATP 结合位点发生突变的另一个显性负突变体（K123A）则使卵孵化过程中断，这种情况可以通过共表达野生型 Ss-RIOK-2 来挽救，但不能通过其 Ss-RIOK-1 同源物来挽救。总的来说，我们的发现表明 Ss-RIOK-2 在致病性蛔虫的发育过程中具有关键和特异性的作用，这可以被用来开发抗感染药物。
