Pyroptotic gasdermin exists in Mollusca and is vital to eliminating bacterial infection

Kunpeng Qin; Shuai Jiang; Hang Xu; Zihao Yuan; Li Sun

doi:10.1016/j.celrep.2023.112414

Pyroptotic gasdermin exists in Mollusca and is vital to eliminating bacterial infection

Cell Rep. 2023 May 30;42(5):112414. doi: 10.1016/j.celrep.2023.112414. Epub 2023 Apr 18.

Authors

Kunpeng Qin¹, Shuai Jiang², Hang Xu¹, Zihao Yuan³, Li Sun⁴

Affiliations

¹ 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.
² 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. Electronic address: sjiang@qdio.ac.cn.
³ 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.
⁴ 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. Electronic address: lsun@qdio.ac.cn.

PMID: 37074912
DOI: 10.1016/j.celrep.2023.112414

Abstract

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.

Keywords: CP: Cell biology; CP: Immunology; Mollusca; caspase; extracellular traps; gasdermin; infection; pyroptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacterial Infections*
Gasdermins*
Mollusca / metabolism
Neoplasm Proteins / metabolism
Pyroptosis / physiology

Substances

Gasdermins
Neoplasm Proteins