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

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

Cell reports 2023 May 30

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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. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Kunpeng Qin, Shuai Jiang, Hang Xu, Zihao Yuan, Li Sun. Pyroptotic gasdermin exists in Mollusca and is vital to eliminating bacterial infection. Cell reports. 2023 May 30;42(5):112414