Palmitoylation-mediated NLRP3 inflammasome activation in teleosts highlights evolutionary divergence in immune regulation  

作　　者：Li Nie Xiang-Yu Wu Zi-Yue Zhao Chen-Jie Fei Ting-Fang Zhu Jian-Zhong Shao Jiong Chen 

机构地区：[1]State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products,School of Marine Sciences,Ningbo University,Ningbo,Zhejiang 315211,China [2]Laboratory of Biochemistry and Molecular Biology,School of Marine Sciences,Ningbo University,Ningbo,Zhejiang 315211,China [3]Key Laboratory of Aquaculture Biotechnology of Ministry of Education,Ningbo University,Ningbo,Zhejiang 315211,China [4]College of Life Sciences,Key Laboratory for Cell and Gene Engineering of Zhejiang Province,Zhejiang University,Hangzhou,Zhejiang 310058,China

出　　处：《Zoological Research》2025年第1期3-14,共12页动物学研究(英文)

基　　金：supported by the National Natural Science Foundation of China (32473194);Natural Science Foundation of Zhejiang Province (LY23C190002);Natural Science Foundation of Ningbo City (202003N4011);One Health Interdisciplinary Research Project of Ningbo University (HZ202201)。

摘　　要：NLRP3 inflammasome activation is pivotal for cytokine secretion and pyroptosis in response to diverse stimuli,playing a crucial role in innate immunity.While extensively studied in mammals,the regulatory mechanisms governing NLRP3 activation in non-mammalian vertebrates remain largely unexplored.Teleosts,as basal vertebrates,represent an ideal model for exploring the evolutionary trajectory of inflammasome regulation.In this study,ABE assays,confocal microscopy,and biochemical analyses were applied to systematically characterize the mechanisms underlying NLRP3 inflammasome in teleosts,using large yellow croakers(Larimichthys crocea,Lc)and zebrafish(Danio rerio,Dr)as representative models.Our findings revealed a previously unrecognized palmitoylation-dependent regulatory mechanism essential for teleost NLRP3 activation.Specifically,zDHHC18-mediated palmitoylation at a teleost-specific cysteine residue(C946 in LcNLRP3,C1037 in DrNLRP3)was required for the translocation of NLRP3 to the dispersed trans-Golgi network,facilitating its subsequent recruitment to the microtubule-organizing center.This membrane trafficking was crucial for inflammasome assembly and downstream inflammatory responses.These findings provide new insights into the distinct regulatory mechanisms of NLRP3 activation in teleosts,highlighting an evolutionary divergence that contributes to innate immunity adaptation in early vertebrates.

关 键 词：NLRP3 PALMITOYLATION zDHHC18 TELEOST Inflammasome activation 

分 类 号：Q958[生物学—动物学]