Pufferfish gasdermin Ea is a significant player in the defense against bacterial pathogens  

作　　者：Hang Xu Kunpeng Qin Kangwei Hao Zihao Yuan Li Sun 

机构地区：[1]CAS and Shandong Province Key Laboratory of Experimental Marine Biology,Institute of Oceanology,CAS Center for Ocean Mega-Science,Chinese Academy of Sciences,Qingdao 266071,China [2]Laboratory for Marine Biology and Biotechnology,Laoshan Laboratory,Qingdao 266237,China [3]School of Marine Science,University of Chinese Academy of Sciences,Qingdao 266400,China

出　　处：《Marine Life Science & Technology》2024年第3期462-474,共13页海洋生命科学与技术（英文）

基　　金：supported by the Science&Tech-nology Innovation Project of Laoshan Laboratory(LSKJ202203000);the Postdoctoral Fellowship Program of CPSF(GZC20232709);the China Postdoctoral Science Foundation(2023TQ0356).

摘　　要：Gasdermins(GSDMs)are proteins cleaved by caspase(CASP)to trigger pyroptosis.In teleosts,pyroptosis is mediated by gasdermin E(GSDME).The Pufferfish,Takifugu rubripes,possesses two GSDME orthologs:named TrGSDMEa and TrGSDMEb.TrGSDMEa is cleaved by CASP3/7 to liberate the N-terminal(NT)domain that can trigger pyroptosis in mammalian cells.However,the biological function of TrGSDMEa in pufferfish is unknown,and TrGSDMEb is poorly studied.We found that TrGSDMEb was cleaved by CASP1/3/6/7/8,but the resulting NT domain,despite its similarity to TrGSDMEa-NT domain in sequence and structure,failed to induce pyroptosis.TrGSDMEa and TrGSDMEb exhibited similar expression patterns in pufferfish under normal physiological conditions but were up-and downregulated,respectively,in expression during Vibrio harveyi and Edwardsiella tarda infection.Bacterial infection induced the activation of TrGSDMEa and CASP3/7 in pufferfish cells,resulting in pyroptosis accompanied with IL-1βproduction and maturation.Inhibition of TrGSDMEa-mediated pyroptosis via TrCASP3/7 reduced the death of pufferfish cells and augmented bacterial dissemination in fish tissues.Structure-oriented mutagenesis identified 16 conserved residues in teleost GSDMEa that were required for the pore formation or auto-inhibition of GSDMEa.This study illustrates the role of GSDMEa-mediated pyroptosis in teleost defense against bacterial pathogens and provides new insights into the structure-based function of vertebrate GSDME.

关 键 词：GSDME CASPASE Takifugu rubripes Bacterial infection Immune defense 

分 类 号：Q178.53[生物学—水生生物学] P714.5[生物学—普通生物学]