Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture and Rural Affairs, Ornamental Aquarium Engineering Research Centre in University of Fujian Province, Fisheries College, Jimei University, Xiamen, Fujian, China.
Key Laboratory of Estuarine Ecological Security and Environmental Health, Tan Kah Kee College, Xiamen University, Zhangzhou, Fujian, China.
Front Immunol. 2023 Jan 13;13:1021443. doi: 10.3389/fimmu.2022.1021443. eCollection 2022.
As a TIR domain-containing molecular, sterile α-and armadillo motif-containing protein (SARM) acts as an adaptor in Toll-like receptor (TLR) signaling, and also plays important roles in mediating apoptosis and neuronal injury. In the present study, the ortholog of , named as , was cloned and identified in large yellow croaker (). The full-length ORF of consists of 2,154 bp, encoding a protein of 717 amino acids (aa), which is comprised of an N-terminal ARM domain, two SAM domains, and a C-terminal TIR domain. Confocal microscopy revealed that -SARM was mainly distributed in the cytoplasm, and the mRNA expression level of was broadly distributed in all the detected organs/tissues, with the highest expression level found in the brain. The expression patterns of could be induced in response to poly I:C, LPS, PGN stimulations, and infection. Notably, although the overexpression of -SARM could significantly induce NF-κB, IRF3, IRF7, and type I IFN promoter activation, whereas the co-expression of SARM with TRIF, -TRAF3, -IRF3, or -IRF7 significantly down-regulated the induction of NF-κB, IRF3, IRF7, or type I IFN promoter activation, and suppressed the antiviral effects as well as the downstream antiviral-related genes expression compared to the only overexpression of -TRIF, -TRAF3, -IRF3, or -IRF7. Co-immunoprecipitation (Co-IP) assays also demonstrated that SARM interacts separately with -TRIF, -TRAF3, -IRF3, and -IRF7. It is thus collectively suggested that -SARM functions as a negative regulator in -TRIF, -TRAF3, and -IRF3/7 involved antiviral signaling.
作为一个 TIR 结构域包含分子，无菌α和装甲蛋白结构域（SARM）作为 Toll 样受体（TLR）信号中的衔接蛋白，在介导细胞凋亡和神经元损伤中也发挥重要作用。在本研究中，克隆并鉴定了大黄鱼（）中的同源物，命名为。的全长 ORF 由 2154bp 组成，编码 717 个氨基酸（aa）的蛋白质，其包含一个 N 端 ARM 结构域，两个 SAM 结构域和一个 C 端 TIR 结构域。共聚焦显微镜显示-SARM 主要分布在细胞质中，并且在所有检测到的器官/组织中广泛表达，在大脑中表达水平最高。可以诱导在 poly I:C、LPS、PGN 刺激和感染的响应中表达。值得注意的是，尽管 -SARM 的过表达可以显著诱导 NF-κB、IRF3、IRF7 和 I 型 IFN 启动子的激活，但是 SARM 与 TRIF、-TRAF3、-IRF3 或 -IRF7 的共表达显著下调了 NF-κB、IRF3、IRF7 或 I 型 IFN 启动子的激活，并抑制了抗病毒作用以及下游抗病毒相关基因的表达，与仅过表达 -TRIF、-TRAF3、-IRF3 或 -IRF7 相比。共免疫沉淀（Co-IP）测定还表明 SARM 分别与 -TRIF、-TRAF3、-IRF3 和 -IRF7 相互作用。因此，总体而言，-SARM 在 -TRIF、-TRAF3 和 -IRF3/7 参与抗病毒信号转导中作为负调节剂发挥作用。
