Gasdermins are executioners of the inflammatory cell death pathway pyroptosis that has so far been studied exclusively in vertebrates. In this study, we identified gasdermin E (GSDME) homologs in several invertebrate species including corals. We report that coral GSDME was cleaved by caspase 3 at two sites, yielding two active isoforms of GSDME N-terminal domain that were capable of inducing pyroptosis. Ectopic coexpression of coral GSDME and caspase 3 in human cells promoted pyroptosis. Corals infected with Vibrio coralliilyticus, a bacterial pathogen causing rapid tissue necrosis of corals worldwide, exhibited necrotic death with elevated caspase 3 activity and GSDME cleavage, whereas inhibition of caspase 3 blocked GSDME cleavage and protected corals from necrotic death. These results indicate that functional gasdermin exists in invertebrates and that coral gasdermin is involved in pathogen-induced coral death. Furthermore, our studies also suggest that mediation of pyroptosis is an evolutionarily conserved function of gasdermins.

Gasdermins 是炎性细胞死亡途径细胞焦亡的刽子手，迄今为止，该途径仅在脊椎动物中进行了研究。在这项研究中，我们在包括珊瑚在内的几种无脊椎动物物种中鉴定了gasdermin E（GSDME）同源物。我们报告说，珊瑚 GSDME 在两个位点被半胱天冬酶 3 切割，产生两种能够诱导细胞焦亡的 GSDME N 端结构域的活性同种型。珊瑚 GSDME 和 caspase 3 在人类细胞中的异位共表达促进细胞焦亡。感染了溶珊瑚弧菌的珊瑚，一种导致全球珊瑚快速组织坏死的细菌病原体，表现出坏死性死亡，半胱天冬酶 3 活性和 GSDME 裂解升高，而半胱天冬酶 3 的抑制阻止 GSDME 裂解并保护珊瑚免于坏死死亡。这些结果表明功能性gasdermin存在于无脊椎动物中，并且珊瑚gasdermin参与病原体诱导的珊瑚死亡。此外，我们的研究还表明，焦亡的介导是 gasdermin 进化上保守的功能。