炎症酶激活的气皮素 D 通过形成膜孔引起热
Xing Liu1,2, Zhibin Zhang1,2, Jianbin Ruan1,3
1Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Nature
|July 8, 2016
概括
气体皮质D-终端片段 (GSDMD-NT) 在细胞膜中形成毛孔,导致热和细胞因子释放. 这个GSDMD-NT片段表现出直接的抗菌活性,可能会影响宿主防御机制.
科学领域:
- 细胞生物学
- 免疫学
- 微生物学
背景情况:
- 在感染和危险信号的响应中激活.
- 激活的体分裂气体皮质D (GSDMD),产生GSDMD-NT,从而诱导热和细胞因子的释放.
- GSDMD-NT诱导细胞死亡的机制以前是未知的.
研究的目的:
- 阐明GSDMD-NT诱导细胞死亡的机制.
- 研究GSDMD-NT的膜结合特性和孔形成活性.
- 确定GSDMD-NT在宿主防御微生物感染中的作用.
主要方法:
- 电子显微镜可视化GSDMD-NT的寡合化和孔隙形成.
- 脂质结合测试以确定GSDMD-NT的相互作用伙伴.
- 位点定向的突变发生,以评估特定残留物在GSDMD-NT功能中的作用.
- 在体外测试以评估GSDMD-NT的杀菌活性.
主要成果:
- GSDMD-NT在膜中寡合,形成电子显微镜可见的孔隙.
- GSDMD-NT与酸丁酸盐,酸丁和心脏脂蛋白结合.
- 保存的基本残留物中的突变消除了GSDMD-NT寡合化,膜结合,孔隙形成和热.
- GSDMD-NT对细胞内成分和细菌具有选择性毒性,不会影响邻近的宿主细胞.
结论:
- 通过形成膜孔,GSDMD-NT诱导热.
- GSDMD-NT的脂质结合特性决定了其杀死细胞的特异性.
- GSDMD-NT具有直接的杀菌活性,有助于宿主防御,尽管其体内重要性需要进一步调查.
相关概念视频
01:17The Extrinsic Apoptotic Pathway
9.2K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.2K
01:31The Intrinsic Apoptotic Pathway
9.1K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.1K
01:11IP3/DAG Signaling Pathway
15.7K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
15.7K
01:16Necrosis
7.1K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
7.1K
01:24Caspases
14.5K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.5K
01:17Phagocytosis of Apoptotic Cells
5.5K
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...
Normal cells contain receptors that prevent them from being recognized...
5.5K