一个棕化-脱棕化继电器在空间时空中控制了 pyroptosis 中的 GSDMD 激活
Na Zhang1,2, Jian Zhang3, Yuanxin Yang1,2
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Nature cell biology
|March 28, 2024
概括
在热致死过程中,Gasdermin D (GSDMD) 的激活是由棕化-脱棕化继电器控制的. 这一过程调节了GSDMD毛孔的形成,影响了宿主防御和败血症的生存.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 生物化学 生化学
背景情况:
- 加斯德明D (GSDMD) 执行 pyroptosis,这是一个编程的细胞死亡,对于对抗感染至关重要.
- GSDMD的激活涉及酶介导的裂变,释放GSDMD-NT形成膜毛孔并释放细胞因子.
- 在烧灭过程中GSDMD的精确空间和时间调节尚未完全理解.
研究的目的:
- 阐明控制气体死过程中Gasdermin D (GSDMD) 激活的调控机制.
- 调查翻译后修改在GSDMD的时空控制中的作用.
主要方法:
- 鉴定GSDMD作为C192.2.的S-palmitoylation的基质.
- 描述DHHC7作为棕酸转移酶和APT2作为涉及的脱棕酶.
- 调节棕细胞代谢/脱棕细胞代谢对热和宿主生存的影响的评估.
主要成果:
- 在烧灭过程中,GSDMD在C192处经历可逆S-palmitoylation.
- 通过DHHC7介导的棕化促进了GSDMD的酶裂变.
- GSDMD-NT的棕化促进了其膜转位,而APT2介导的棕化推动了孔隙形成.
结论:
- 一个棕化-脱棕化继电器空间时空地控制GSDMD的激活.
- 破坏这种继电器会抑制热亡,在致命的败血症休克模型中提高生存率.
- 这种机制对于对病原体进行有效的宿主防御至关重要.
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