Department of Zoology, University of Delhi, Delhi, India.
Department of Zoology, Maitreyi College, University of Delhi, Delhi, India.
Fish Shellfish Immunol. 2024 Nov;154:109916. doi: 10.1016/j.fsi.2024.109916. Epub 2024 Sep 20.
NOD1, plays a pivotal role in immune responses against bacterial as well as viral invasions. While the downstream signaling pathway of NOD1 is well understood in mammals, its characterization in lower vertebrates remains elusive. In present study, an effort was made to identify and characterize downstream signaling cascade of NOD1 in response to LPS, a potential ligand of NOD1 in teleosts, in spotted snakehead. In addition, the temporal effect of LPS on transcriptional modulation of NOD1 and its downstream signaling molecule RIPK2 was investigated. Docking studies revealed well conserved leucine rich domains of NOD1 that could bind with LPS. Further, NACHT-ATP interactions revealed differences in ATP binding motifs within the NACHT domain in spotted snakehead compared to those reported in other fish species and mammals pointing towards species-specific nature of ATP interactions within the NACHT domain. Further, it was revealed that the ssNOD1-CARD domain interacts with the CARD domain of downstream signaling molecule ssRIPK. Interestingly, LPS treatment modulated the expression of both, ssNOD1 and ssRIPK2 in a time-dependent manner.
NOD1 在免疫反应中起着关键作用,可对抗细菌和病毒的入侵。虽然哺乳动物中 NOD1 的下游信号通路已得到充分研究,但在低等脊椎动物中的特征仍然难以捉摸。在本研究中,我们努力鉴定和描述 NOD1 在斑点蛇头鱼中对 LPS(一种潜在的 NOD1 配体)的下游信号级联反应,同时还研究了 LPS 对 NOD1 及其下游信号分子 RIPK2 转录调控的时间效应。对接研究表明,NOD1 的富含亮氨酸结构域与 LPS 结合良好。此外,NACHT-ATP 相互作用揭示了斑点蛇头鱼 NACHT 结构域内的 ATP 结合基序与其他鱼类和哺乳动物报道的基序存在差异,这表明 NACHT 结构域内的 ATP 相互作用具有物种特异性。此外,结果表明 ssNOD1-CARD 结构域与下游信号分子 ssRIPK 的 CARD 结构域相互作用。有趣的是,LPS 处理以时间依赖性方式调节 ssNOD1 和 ssRIPK2 的表达。