Pyroptotic gasdermin exists in Mollusca and is vital to eliminating bacterial infection
Kunpeng Qin,
Shuai Jiang,
Hang Xu,
Zihao Yuan,
Li Sun
Affiliations
Kunpeng Qin
CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing, China
Shuai Jiang
CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing, China; Corresponding author
Hang Xu
CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing, China
Zihao Yuan
CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China
Li Sun
CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China; College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing, China; Corresponding author
Summary: Gasdermin (GSDM) is a family of proteins that execute pyroptosis in vertebrate. In invertebrate, pyroptotic GSDM was documented only in coral. Recent studies identified abundant GSDM structural homologs in Mollusca, but their functions are unclear. Herein, we report a functional GSDM from Pacific abalone Haliotis discus (HdGSDME). HdGSDME is specifically activated by abalone caspase 3 (HdCASP3) cleavage at two distinct sites, generating two active isoforms with pyroptotic and cytotoxic activities. HdGSDME possesses evolutionarily conserved residues that proved to be essential to the N-terminal pore-formation and C-terminal auto-inhibition capacities. Bacterial challenge activates the HdCASP3-HdGSDME pathway and induces pyroptosis and extracellular traps in abalone. Blockage of the HdCASP3-HdGSDME axis promotes bacterial invasion and host mortality. Collectively, this study reveals the existence of functionally conserved and yet distinct-featured GSDM in Mollusca and provides insights into the function and evolution of invertebrate GSDM.
