Yan Baolong, Sun Weiwei, Shi Xiaomeng, Huang Liyang, Chen Lingzi, Wang Suhua, Yan Lanzhu, Liang Shaohui, Huang Huicong
Department of Parasitology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Department of Biochemistry, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Vet Parasitol. 2017 Jun 15;240:1-10. doi: 10.1016/j.vetpar.2017.04.025. Epub 2017 Apr 25.
The insulin-like signaling (IIS) pathway is considered to be significant in regulating fat metabolism, dauer formation, stress response and longevity in Caenorhabditis elegans. "Dauer hypothesis" indicates that similar IIS transduction mechanism regulates dauer development in free-living nematode C. elegans and the development of infective third-stage larvae (iL3) in parasitic nematodes, and this is bolstered by a few researches on structures and functions of the homologous genes in the IIS pathway cloned from several parasitic nematodes. In this study, we identified the insulin-like receptor encoding gene, Acan-daf-2, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. The sequence of Acan-DAF-2, consisting of 1413 amino acids, contained all of the characteristic domains of insulin-like receptors from other taxa. The expression patterns of Acan-daf-2 in the C. elegans surrogate system showed that pAcan-daf-2:gfp was only expressed in intestine, compared with the orthologue in C. elegans, Ce-daf-2 in both intestine and neurons. In addition to the similar genomic organization to Ce-daf-2, Acan-DAF-2 could also negatively regulate Ce-DAF-16A through nuclear/cytosolic translocation and partially restore the C. elegans daf-2(e1370) mutation in longevity, dauer formation and stress resistance. These findings provided further evidence of the functional conservation of DAF-2 between parasitic nematodes and the free-living nematode C. elegans, and might be significant in understanding the developmental biology of nematode parasites, particularly in the infective process and the host-specificity.
胰岛素样信号（IIS）通路在调节秀丽隐杆线虫的脂肪代谢、滞育形成、应激反应和寿命方面被认为具有重要意义。“滞育假说”表明，类似的IIS转导机制调节自由生活线虫秀丽隐杆线虫的滞育发育以及寄生线虫感染性三期幼虫（iL3）的发育，并且从几种寄生线虫中克隆的IIS通路中同源基因的结构和功能的一些研究支持了这一点。在本研究中，我们从寄生线虫广州管圆线虫中鉴定出胰岛素样受体编码基因Acan-daf-2，并在寿命、抗逆性和滞育形成方面更深入地确定了其基因组结构、转录本和功能。Acan-DAF-2序列由1413个氨基酸组成，包含来自其他分类群的胰岛素样受体的所有特征结构域。Acan-daf-2在秀丽隐杆线虫替代系统中的表达模式表明，与秀丽隐杆线虫中的直系同源基因Ce-daf-2在肠道和神经元中均有表达不同，pAcan-daf-2:gfp仅在肠道中表达。除了与Ce-daf-2具有相似的基因组组织外，Acan-DAF-2还可以通过核/细胞质转位负向调节Ce-DAF-16A，并在寿命、滞育形成和抗逆性方面部分恢复秀丽隐杆线虫daf-2(e1370)突变。这些发现为寄生线虫和自由生活线虫秀丽隐杆线虫之间DAF-2的功能保守性提供了进一步证据，并且可能在理解线虫寄生虫的发育生物学，特别是在感染过程和宿主特异性方面具有重要意义。
