Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: https://twitter.com/Anh_Immunology.
Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA 02115, USA.
J Mol Biol. 2022 Feb 28;434(4):167427. doi: 10.1016/j.jmb.2021.167427. Epub 2021 Dec 29.
Gasdermins are proteins that can self-assemble into membrane channels (also known as pores). These pores can serve as conduits for the secretion of cytosolic molecules, with the most commonly studied being members of the interleukin-1 family of cytokines. However, gasdermin pore forming activities must be tightly regulated, as the channels that they form can lead to a lytic form of cell death known as pyroptosis. Recent studies have revealed multiple mechanisms that control gasdermin activities within cells and identified gasdermin proteins in organisms as diverse as bacteria, humans and yeast. In this Review, we discuss the molecular and cellular mechanisms that regulate gasdermin pore formation. These mechanisms of gasdermin regulation likely explain the flexibility of these proteins to display cell type specific (and potentially organism specific) functions.
Gasdermins 是能够自我组装成膜通道(也称为孔)的蛋白质。这些孔可以作为细胞质分子分泌的通道,其中最常研究的是白细胞介素-1 家族细胞因子的成员。然而,Gasdermin 孔形成活性必须受到严格控制,因为它们形成的通道可能导致一种称为细胞焦亡的溶细胞形式的细胞死亡。最近的研究揭示了控制细胞内 Gasdermin 活性的多种机制,并在细菌、人类和酵母等多种生物中鉴定出了 Gasdermin 蛋白。在这篇综述中,我们讨论了调节 Gasdermin 孔形成的分子和细胞机制。这些 Gasdermin 调节机制可能解释了这些蛋白质显示细胞类型特异性(并且可能是生物体特异性)功能的灵活性。