Conservation of eATP perception throughout multicellular animal evolution: Identification and functional characterization of coral and amphioxus P2X7-like receptors and flounder P2X7 receptor
Conservation of eATP perception throughout multicellular animal evolution: Identification and functional characterization of coral and amphioxus P2X7-like receptors and flounder P2X7 receptor
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DOI：
10.1016/j.dci.2020.103641
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发表时间：
2020-05-01
影响因子：
2.9
通讯作者：
Zhang, Shicui
中科院分区：
文献类型：
--
作者：
Duan, Huimin;Ni, Shousheng;Zhang, Shicui
细胞外ATP（eATP）是一种常见的内源性损伤相关分子模式，通过其受体P2 X7 R感知。eATP/P2 X7 R信号是否在整个动物进化过程中保守尚不清楚。此外，目前关于无脊椎动物中P2 X7 R的信息很少。在这里，我们证明了珊瑚P2 X7-like受体，AdP 2X 7 RL，文昌鱼P2 X7-like受体，BjP 2X 7 RL和比目鱼P2 X7受体，PoP 2X 7 R，共享哺乳动物P2 X7 R的共同特征，其三维结构显示出与人类P2 X7 R的高度相似性。Adp 2x 7 rl、Bjp 2x 7 rl和Pop 2x 7 r的表达均受LPS和ATP的调节。AdP 2X 7 RL、BjP 2X 7 RL和PoP 2X 7 R在表达AdP 2X 7 RL、BjP 2X 7 RL和PoP 2X 7 R的HEK细胞中分布于细胞膜上，并与eATP有较强的亲和力。重要的是，AdP 2X 7 RL、BjP 2X 7 RL和PoP 2X 7 R与eATP的结合都诱导了类似的下游反应，包括诱导细胞因子（IL-1 β、IL-6、IL-8和CCL-2）、增强吞噬作用和激活哺乳动物P2 X7 R观察到的AKT/ERK相关信号通路。总的来说，我们的研究结果首次表明，珊瑚和文昌鱼P2 X7 RL以及比目鱼P2 X7 R可以与eATP相互作用，并诱导触发哺乳动物机制的事件，这表明在多细胞动物进化过程中eATP感知的高度保守性。
Perception of extracellular ATP (eATP), a common endogenous damage-associated molecular pattern, is through its receptor P2X7R. If eATP/P2X7R signaling is conserved throughout animal evolution is unknown. Moreover, little information is currently available regarding P2X7R in invertebrates. Here we demonstrated that the coral P2X7-like receptor, AdP2X7RL, the amphioxus P2X7-like receptor, BjP2X7RL and the flounder P2X7 receptor, PoP2X7R, shared common features characteristic of mammalian P2X7R, and their 3D structures displayed high resemblance to that of human P2X7R. Expression of Adp2x7rl, Bjp2x7rl and Pop2x7r was all subjected to the regulation by LPS and ATP. We also showed that AdP2X7RL, BjP2X7RL and PoP2X7R were distributed on the plasma membrane in AdP2X7RL-, BjP2X7RL- and PoP2X7R-expressing HEK cells, and had strong affinity to eATP. Importantly, the binding of AdP2X7RL, BjP2X7RL and PoP2X7R to eATP all induced similar downstream responses, including induction of cytokines (IL-1 beta, IL-6, IL-8 and CCL-2), enhancement of phagocytosis and activation of AKT/ERK-associated signaling pathway observed for mammalian P2X7R. Collectively, our results indicate for the first time that both coral and amphioxus P2X7RL as well as flounder P2X7R can interact with eATP, and induce events that trigger mammalian mechanisms, suggesting the high conservation of eATP perception throughout multicellular animal evolution.