As the executor of pyroptosis known to date, gasdermins (GSDMs), consists of GSDMA, GSDMB, GSDMC, GSDMD, GSDME and pejvakin, might play critical roles in anti-bacterial infection as well as inflammatory diseases. However, zebrafish only harbors a pair of Gsdme (Gsdmea/b), and their activation mechanisms remain largely unknown. Herein, we investigate the activation mechanism of Gsdmea/b cleaved by inflammatory and apoptotic caspases in zebrafish，and found that Gsdmea/b are equally cleaved by Caspase 19b, a sister of Caspy2, but not Caspy. Moreover, the zebrafish apoptotic effector caspases, including Caspase 3a/b and Caspase 7, also can cleave Gsdmea/b at the same sites as inflammatory caspases recognized. Importantly, our results reveal that Caspase 8a/b can cleave Gsdmeb, but only Caspase 8a can cleave Gsdmea. Taken together, these findings suggest that zebrafish Gsdmea/b can concurrently function as GSDMD and GSDME in mammals, which will contribute to better understanding the mechanism of pyroptosis activation in teleost, as well as provide a clue for drug screening model against inflammatory diseases.

作为迄今为止已知的细胞焦亡的执行者，gasdermins (GSDMs) 由 GSDMA、GSDMB、GSDMC、GSDMD、GSDME 和 pejvakin 组成，可能在抗菌感染和炎症性疾病中发挥关键作用。然而，斑马鱼只有一对 Gsdme (Gsdmea/b)，它们的激活机制在很大程度上仍然未知。在此，我们研究了斑马鱼中炎症和凋亡半胱天冬酶切割 Gsdmea/b 的激活机制，发现 Gsdmea/b 被 Caspy2 的姐妹 Caspase 19b 同等切割，但不是 Caspy。此外，斑马鱼凋亡效应半胱天冬酶，包括半胱天冬酶 3a/b 和半胱天冬酶 7，也可以在识别炎性半胱天冬酶的相同位点切割 Gsdmea/b。重要的是，我们的结果表明 Caspase 8a/b 可以切割 Gsdmeb，但只有 Caspase 8a 可以切割 Gsdmea。综合起来，