The gasdermins are a family of recently identified pore-forming effector proteins that cause membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. Gasdermins contain a cytotoxic N-terminal domain and a C-terminal repressor domain connected by a flexible linker. Proteolytic cleavage between these two domains releases the intramolecular inhibition on the cytotoxic domain, allowing it to insert into cell membranes and form large oligomeric pores, which disrupts ion homeostasis and induces cell death. Gasdermin-induced pyroptosis plays a prominent role in many hereditary diseases and (auto)inflammatory disorders as well as in cancer. In this Review, we discuss recent developments in gasdermin research with a focus on mechanisms that control gasdermin activation, pore formation and functional consequences of gasdermin-induced membrane permeabilization.

中文翻译：

---

Gasdermins是执行细胞死亡和炎症的蛋白质家族。

胃泌素是最近发现的致孔蛋白家族，可引起膜通透性和细胞凋亡，这是一种裂解性促炎性细胞死亡。胃泌素含有通过柔性接头连接的细胞毒性N末端结构域和C末端阻遏物结构域。这两个结构域之间的蛋白水解切割释放了对细胞毒性结构域的分子内抑制作用，使其能够插入细胞膜并形成大的寡聚孔，从而破坏了离子稳态并诱导了细胞死亡。加德明诱导的细胞凋亡在许多遗传性疾病和（自体）炎症性疾病以及癌症中起着重要作用。在本评论中，我们将讨论加德敏研究的最新进展，重点是控制加德敏激活的机制，