文献类型：期刊文献

英文题名：Cleavage of gasdermin by apoptotic caspases triggers pyroptosis restricting bacterial colonization in Hydra

作者：Li, Shuxin[1];Lin, Xiuqing[1];Zhang, Yuanxing[2,3];Liu, Qin[1,2,3];Chen, Shouwen[1]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Southern Marine Sci & Engn Guangdong Lab Zhuhai, Zhuhai 519000, Peoples R China;[3]Shanghai Engn Res Ctr Marine Cultured Anim Vaccine, Shanghai 200237, Peoples R China

年份：2024

卷号：155

外文期刊名：DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001199549800001)】；

基金：We thank XB Hu, JM Xu, SL Gu, YZ Chen for their assistance with microscope and W Wu, JM Xu for their assistance with Hydra experi- ment. This work was supported by the NSFC (No. 32002429) to S.C., the China Postdoctoral Science Foundation (No. 2020M671033) to S.C., and The Fundamental Research Funds for the Central Universities (No. 222201231721) to Q.L.

语种：英文

外文关键词：Gasdermin; GSDME; Evolution; Recognition motif; Hydra

摘要：Gasdermin (GSDM) proteins, as the direct executors of pyroptosis, are structurally and functionally conserved among vertebrates and play crucial roles in host defense against infection, inflammation, and cancer. However, the origin of functional GSDMs remains elusive in the animal kingdom. Here, we found that functional GSDME homologs first appeared in the cnidarian. Moreover, these animal GSDME homologs share evolutionarily conserved apoptotic caspase cleavage sites. Thus, we verified the functional conservation of apoptotic caspaseGSDME cascade in Hydra, a representative species of cnidarian. Unlike vertebrate GSDME homologs, HyGSDME could be cleaved by four Hydra caspase homologs with caspase-3 activity at two sites. Furthermore, in vivo activation of Hydra caspases resulted in HyGSDME cleavage to induce pyroptosis, exacerbating injury and restricting bacterial burden, which protects Hydra from pathogen invasion. In conclusion, these results suggest that GSDME-dependent pyroptosis may be an ancient and conserved host defense mechanism, which may contribute to better understanding on the origin and evolution of GSDMs.