State Key Laboratory of Agricultural Microbiology, Key Laboratory of Development of Veterinary Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Faculty of Veterinary and Agricultural Sciences, Department of Veterinary Biosciences, The University of Melbourne, Parkville, VIC, Australia.
FASEB J. 2020 Feb;34(2):2075-2086. doi: 10.1096/fj.201900888RR. Epub 2019 Dec 27.
In the free-living nematode Caenorhabditis elegans, the serine/threonine-specific protein kinase, AKT, is known to play a key role in dauer formation, life-span, and stress-resistance through the insulin-like signaling pathway. Although the structure and function of AKT-coding genes of C. elegans are understood, this is not the case for homologous genes in parasitic nematodes. In the present study, we explored a C. elegans akt-1 gene homolog in the parasitic nematode Haemonchus contortus, investigated its transcript isoforms (Hc-akt-1a and Hc-akt-1b), and studied expression and function using both homologous and heterologous functional genomic tools. In C. elegans, we showed that the predicted promoter of Hc-akt-1 drives substantial expression in ASJ neurons of the N2 (wild-type) strain. In H. contortus (Haecon-5 stain), RNAi (soaking) led to a significantly decreased transcript abundance for both Hc-akt-1a and Hc-akt-1b, and reduced larval development in larval stages in vitro. Chemical inhibition was also shown to block larval development. Taken together, the evidence from this study points to a key functional role for Hc-akt-1 in H. contortus.
在自由生活的线虫秀丽隐杆线虫中，丝氨酸/苏氨酸特异性蛋白激酶 AKT 通过胰岛素样信号通路在 dauer 形成、寿命和抗应激中发挥关键作用。尽管秀丽隐杆线虫 AKT 编码基因的结构和功能是已知的，但寄生线虫中的同源基因并非如此。在本研究中，我们在寄生线虫旋毛虫中探索了秀丽隐杆线虫 akt-1 基因的同源物，研究了其转录异构体（Hc-akt-1a 和 Hc-akt-1b），并使用同源和异源功能基因组工具研究了其表达和功能。在秀丽隐杆线虫中，我们表明 Hc-akt-1 的预测启动子在 N2（野生型）菌株的 ASJ 神经元中驱动大量表达。在旋毛虫（Haecon-5 株）中，RNAi（浸泡）导致 Hc-akt-1a 和 Hc-akt-1b 的转录丰度显著降低，体外幼虫阶段的幼虫发育减少。化学抑制也被证明可以阻断幼虫发育。综上所述，本研究的证据表明 Hc-akt-1 在旋毛虫中具有关键的功能作用。
