State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, 200237, China.
Fish Shellfish Immunol. 2020 May;100:324-333. doi: 10.1016/j.fsi.2020.03.032. Epub 2020 Mar 18.
Apoptosis-associated speck-like protein containing a C-terminal caspase recruit domain (ASC) is an important adapter protein in the inflammasome complex that mediates inflammatory caspase activation and host innate immunity in mammals. However, the function of inflammasome components in lower vertebrate remains poorly understood. In this study, full length of SmASC was cloned from turbot (Scophthalmus maximus). Through bioinformatic analysis, we found that SmASC shares relatively high identity with ASC in bony fish. Furthermore, we found that the intact SmASC can form an oligomeric speck-like structure, while the PYD segment of SmASC can form the filamentous structure. Moreover, expression of SmASC was induced after intraperitoneal injection of Edwardsiella piscicida (E. piscicida) in vivo. To further explore the role of SmASC during infection, we constructed SmASC knockdown and overexpression models by administration of siRNA and overexpression plasmids in vivo, respectively. Expression of SmASC decreased the propagation of E. piscicida in different immune organs. In summary, our results characterize the function of SmASC in S. maximus, suggesting that the SmASC plays a critical role in turbot immune responses.
凋亡相关斑点样蛋白包含一个 C 末端半胱天冬酶募集结构域 (ASC)，是炎症小体复合物中的一种重要衔接蛋白，在哺乳动物中介导炎症性半胱天冬酶激活和宿主固有免疫。然而，炎症小体成分在低等脊椎动物中的功能仍知之甚少。本研究从大菱鲆（Scophthalmus maximus）中克隆了全长 SmASC。通过生物信息学分析，我们发现 SmASC 与硬骨鱼中的 ASC 具有相对较高的同源性。此外，我们发现完整的 SmASC 可以形成寡聚斑点样结构，而 SmASC 的 PYD 片段可以形成丝状结构。此外，体内注射爱德华氏菌（Edwardsiella piscicida，E. piscicida）后 SmASC 的表达被诱导。为了进一步探讨 SmASC 在感染过程中的作用，我们通过体内注射 siRNA 和过表达质粒分别构建了 SmASC 敲低和过表达模型。SmASC 的表达降低了 E. piscicida 在不同免疫器官中的繁殖。综上所述，我们的研究结果阐明了 SmASC 在大菱鲆中的功能，表明 SmASC 在大菱鲆免疫反应中发挥着关键作用。
