Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Semin Immunol. 2023 Sep;69:101803. doi: 10.1016/j.smim.2023.101803. Epub 2023 Jul 10.
The family of gasdermin proteins plays a key role in the host response against external and internal pathogenic signals by mediating the form of inflammatory regulated cell death known as pyroptosis. One of the most well-studied gasdermins within innate immunity is gasdermin D, which is cleaved, oligomerizes, and forms plasma membrane pores. Gasdermin D pores lead to a number of downstream cellular consequences including plasma membrane rupture, or cell lysis. In this review, we describe mechanisms of activation for each of the gasdermins, their cell type specificity and some disease associations. We then discuss downstream consequences of gasdermin pore formation, including cellular mechanisms of membrane repair. Finally, we present some important next steps to better understand pyroptosis and the cellular consequences of gasdermin pore formation.
gasdermin 蛋白家族在宿主对内外源性致病信号的反应中发挥着关键作用,通过介导一种被称为细胞焦亡的炎症调节性细胞死亡形式。gasdermin D 是先天免疫中研究最广泛的 gasdermin 蛋白之一,它可以被切割、寡聚化并形成质膜孔。gasdermin D 孔导致许多下游细胞后果,包括质膜破裂或细胞裂解。在这篇综述中,我们描述了每种 gasdermin 的激活机制、它们的细胞类型特异性和一些疾病关联。然后,我们讨论了 gasdermin 孔形成的下游后果,包括膜修复的细胞机制。最后,我们提出了一些重要的下一步措施,以更好地理解细胞焦亡和 gasdermin 孔形成的细胞后果。