小柯机器人

美国哈佛医学院Philip J. Kranzusch研究组发现，cGLR是先天性免疫中一个多样化的模式识别受体家族。相关论文于2023年6月27日在线发表在《细胞》杂志上。

研究人员表示，环状GMP-AMP合成酶（cGAS）是人体细胞中的一种酶，控制对细胞膜DNA的免疫反应。结合DNA后，cGAS合成一个核苷酸信号2′3′-cGAMP，激活STING依赖的下游免疫力。

研究人员发现cGAS样受体（cGLR）构成了先天免疫中一个主要的模式识别受体家族。在最近果蝇分析的基础上，研究人员确定了超过3000个cGLR存在于几乎所有的后生动物门。对150个动物cGLR的正向生化筛选显示了一个保守的信号传递机制，包括对dsDNA和dsRNA配体的反应以及核苷酸信号cGAMP、c-UMP-AMP和c-di-AMP的合成。结合珊瑚和牡蛎动物的结构生物学和体内分析，研究人员解释了不同核苷酸信号的合成如何使细胞控制离散的cGLR-STING信号通路。这些结果揭示了cGLR是一个广泛的模式识别受体家族，并建立了管理动物免疫中核苷酸信号的分子规则。

附：英文原文

Title: cGLRs are a diverse family of pattern recognition receptors in innate immunity

Author: Yao Li, Kailey M. Slavik, Hunter C. Toyoda, Benjamin R. Morehouse, Carina C. de Oliveira Mann, Anamaria Elek, Shani Levy, Zhenwei Wang, Kepler S. Mears, Jingjing Liu, Dmitry Kashin, Ximing Guo, Tali Mass, Arnau Sebé-Pedrós, Frank Schwede, Philip J. Kranzusch

Issue&Volume: 2023-06-27

Abstract: Cyclic GMP-AMP synthase (cGAS) is an enzyme in human cells that controls an immune response to cytosolic DNA. Upon binding DNA, cGAS synthesizes a nucleotide signal 2′3′-cGAMP that activates STING-dependent downstream immunity. Here, we discover that cGAS-like receptors (cGLRs) constitute a major family of pattern recognition receptors in innate immunity. Building on recent analysis in Drosophila, we identify >3,000 cGLRs present in nearly all metazoan phyla. A forward biochemical screening of 150 animal cGLRs reveals a conserved mechanism of signaling including response to dsDNA and dsRNA ligands and synthesis of isomers of the nucleotide signals cGAMP, c-UMP-AMP, and c-di-AMP. Combining structural biology and in vivo analysis in coral and oyster animals, we explain how synthesis of distinct nucleotide signals enables cells to control discrete cGLR-STING signaling pathways. Our results reveal cGLRs as a widespread family of pattern recognition receptors and establish molecular rules that govern nucleotide signaling in animal immunity.

DOI: 10.1016/j.cell.2023.05.038

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00590-1