赛普特蛋白通过调控气敏D的裂解和ninjurin-1介导的质膜破裂促进巨噬细胞的脓毒症

IF 6.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Dominik Brokatzky , Margarida C. Gomes , Stevens Robertin , Carolina Albino , Sydney L. Miles , Serge Mostowy
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引用次数: 0

摘要

人们主要了解隔膜细胞骨架在细胞分裂和宿主防御细菌感染中的作用。尽管最近有了新的认识,但人们对隔膜在宿主防御中的全部作用还知之甚少。在巨噬细胞中,志贺氏杆菌会诱导热噬,这是一种促炎性细胞死亡形式,依赖于质膜上的 gasdermin D(GSDMD)孔和细胞表面蛋白 ninjurin-1(NINJ1)使膜破裂。在这里,我们发现隔蛋白能促进巨噬细胞在脂多糖(LPS)/尼革菌素和志贺氏杆菌感染诱导下的热休克,但不影响细胞因子的表达或释放。我们观察到,隔蛋白丝在细胞质膜上聚集,而GSDMD的裂解在隔蛋白缺失的细胞中受损。我们发现,隔膜调节线粒体动力学和 NINJ1 的表达。通过志贺氏菌-斑马鱼感染模型,我们发现隔蛋白介导的热蛋白沉积是一种体内感染控制机制。发现隔蛋白是热蛋白沉积的介质可能会激发创新的抗菌和抗炎治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Septins promote macrophage pyroptosis by regulating gasdermin D cleavage and ninjurin-1-mediated plasma membrane rupture

Septins promote macrophage pyroptosis by regulating gasdermin D cleavage and ninjurin-1-mediated plasma membrane rupture

Septins promote macrophage pyroptosis by regulating gasdermin D cleavage and ninjurin-1-mediated plasma membrane rupture

The septin cytoskeleton is primarily known for roles in cell division and host defense against bacterial infection. Despite recent insights, the full breadth of roles for septins in host defense is poorly understood. In macrophages, Shigella induces pyroptosis, a pro-inflammatory form of cell death dependent upon gasdermin D (GSDMD) pores at the plasma membrane and cell surface protein ninjurin-1 (NINJ1) for membrane rupture. Here, we discover that septins promote macrophage pyroptosis induced by lipopolysaccharide (LPS)/nigericin and Shigella infection, but do not affect cytokine expression or release. We observe that septin filaments assemble at the plasma membrane, and cleavage of GSDMD is impaired in septin-depleted cells. We found that septins regulate mitochondrial dynamics and the expression of NINJ1. Using a Shigella-zebrafish infection model, we show that septin-mediated pyroptosis is an in vivo mechanism of infection control. The discovery of septins as a mediator of pyroptosis may inspire innovative anti-bacterial and anti-inflammatory treatments.

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来源期刊
Cell Chemical Biology
Cell Chemical Biology Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
14.70
自引率
2.30%
发文量
143
期刊介绍: Cell Chemical Biology, a Cell Press journal established in 1994 as Chemistry & Biology, focuses on publishing crucial advances in chemical biology research with broad appeal to our diverse community, spanning basic scientists to clinicians. Pioneering investigations at the chemistry-biology interface, the journal fosters collaboration between these disciplines. We encourage submissions providing significant conceptual advancements of broad interest across chemical, biological, clinical, and related fields. Particularly sought are articles utilizing chemical tools to perturb, visualize, and measure biological systems, offering unique insights into molecular mechanisms, disease biology, and therapeutics.
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