首页|Pufferfish gasdermin Ea is a significant player in the defense against bacterial pathogens
Pufferfish gasdermin Ea is a significant player in the defense against bacterial pathogens
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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-1β production and maturation.Inhibition of TrGSDMEa-mediated pyroptosis via TrCASP3/7 reduced the death of pufferfish cells and augmented bacterial dissemina-tion 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.
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
Laboratory for Marine Biology and Biotechnology,Laoshan Laboratory,Qingdao 266237,China
School of Marine Science,University of Chinese Academy of Sciences,Qingdao 266400,China
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