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石斑鱼 cGAS 是一种负调控 STING 介导的干扰素反应的蛋白。

Grouper cGAS is a negative regulator of STING-mediated interferon response.

机构信息

College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China.

Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, Zhanjiang, China.

出版信息

Front Immunol. 2023 Feb 7;14:1092824. doi: 10.3389/fimmu.2023.1092824. eCollection 2023.

DOI:10.3389/fimmu.2023.1092824
PMID:36845102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9945316/
Abstract

Cyclic GMP-AMP synthase (cGAS) is one of the classical pattern recognition receptors that recognizes mainly intracytoplasmic DNA. cGAS induces type I IFN responses to the cGAS-STING signaling pathway. To investigate the roles of cGAS-STING signaling pathway in grouper, a cGAS homolog (named EccGAS) was cloned and identified from orange-spotted grouper (). The open reading frame (ORF) of EccGAS is 1695 bp, encodes 575 amino acids, and contains a Mab-21 typical structural domain. EccGAS is homologous to and humans at 71.8% and 41.49%, respectively. EccGAS mRNA is abundant in the blood, skin, and gills. It is uniformly distributed in the cytoplasm and colocalized in the endoplasmic reticulum and mitochondria. Silencing of EccGAS inhibited the replication of Singapore grouper iridovirus (SGIV) in grouper spleen (GS) cells and enhanced the expression of interferon-related factors. Furthermore, EccGAS inhibited EcSTING-mediated interferon response and interacted with EcSTING, EcTAK1, EcTBK1, and EcIRF3. These results suggest that EccGAS may be a negative regulator of the cGAS-STING signaling pathway of fish.

摘要

环鸟苷酸-腺苷酸合酶（cGAS）是一种经典的模式识别受体，主要识别细胞内 DNA。cGAS 通过 cGAS-STING 信号通路诱导 I 型 IFN 反应。为了研究 cGAS-STING 信号通路在石斑鱼中的作用，从鞍带石斑鱼（）中克隆并鉴定了一种 cGAS 同源物（命名为 EccGAS）。EccGAS 的开放阅读框（ORF）为 1695bp，编码 575 个氨基酸，含有一个 Mab-21 典型结构域。EccGAS 与 和人类的同源性分别为 71.8%和 41.49%。EccGAS mRNA 在血液、皮肤和鳃中丰富表达。它均匀分布在细胞质中，并与内质网和线粒体共定位。EccGAS 的沉默抑制了石斑鱼脾脏（GS）细胞中新加坡石斑鱼虹彩病毒（SGIV）的复制，并增强了干扰素相关因子的表达。此外，EccGAS 抑制了 EcSTING 介导的干扰素反应，并与 EcSTING、EcTAK1、EcTBK1 和 EcIRF3 相互作用。这些结果表明，EccGAS 可能是鱼类 cGAS-STING 信号通路的负调控因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/782688f8603b/fimmu-14-1092824-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/dc6f5604469e/fimmu-14-1092824-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/b1d195a607e3/fimmu-14-1092824-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/e5cf56e6159b/fimmu-14-1092824-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/17e1c9eaa609/fimmu-14-1092824-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/04b84eb06a5b/fimmu-14-1092824-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/c3dad3d2a99b/fimmu-14-1092824-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/782688f8603b/fimmu-14-1092824-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/dc6f5604469e/fimmu-14-1092824-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/b1d195a607e3/fimmu-14-1092824-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/e5cf56e6159b/fimmu-14-1092824-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/17e1c9eaa609/fimmu-14-1092824-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/04b84eb06a5b/fimmu-14-1092824-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/c3dad3d2a99b/fimmu-14-1092824-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca09/9945316/782688f8603b/fimmu-14-1092824-g007.jpg

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cGASa and cGASb from grass carp (Ctenopharyngodon idellus) play opposite roles in mediating type I interferon response.草鱼（Ctenopharyngodon idellus）的cGASa和cGASb在介导I型干扰素反应中发挥相反作用。
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