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在非哺乳动物中,Caspase-1激活了gasdermin A
Zachary Paul Billman1,2, Stephen Bela Kovacs1,2, Bo Wei1
1Department of Integrative Immunobiology; Molecular Genetics and Microbiology; Pathology; and Cell Biology, Duke University School of Medicine, Durham, United States.
eLife
|March 18, 2024
概括
气体皮质激素会触发热,一种细胞死亡形式. 进化分析显示,caspase-1在不同物种中反复转移其气皮标,从鱼类中的GSDME到鸟类中的GSDMA和哺乳动物中的GSDMD.
科学领域:
- 免疫学 免疫学 免疫学
- 进化生物学 进化生物学
- 细胞生物学 细胞生物学
背景情况:
- 气体膜是热的关键媒介,这是一个受调节的细胞死亡途径.
- 哺乳动物拥有五种气皮膜 (GSDMA-E),这些气皮膜由诸如caspases和granzymes之类的蛋白酶激活.
- 对于GSDMA的激活途径在很大程度上是未知的.
研究的目的:
- 为了对气皮蛋白家族进行全面的进化分析.
- 为了阐明通过caspases激活gasdermin的进化历史.
- 了解卡斯帕-1在进化过程中对不同气皮标的变异特异性.
主要方法:
- 跨脊椎动物的gasdermin基因家族的比较进化分析.
- 在气体皮质蛋白内识别和比较酶裂解部位.
- 生物化学试验测试来自不同物种的GSDMA的酶-1裂变.
主要成果:
- 早期两动物/爬行动物/鸟类中GSDMA的基因重复导致哺乳动物中的GSDMA-D.
- 两动物,爬行动物和鸟类GSDMA具有caspase-1分离点 (例如,YVAD,FASD),与哺乳动物GSDMA不同.
- 来自鸟类,两动物和爬行动物的caspase-1分裂GSDMA,而哺乳动物的caspase-1通过外体相互作用准GSDMD.
结论:
- 卡斯巴-1与气皮膜有着长期但不断发展的关联.
- 在脊椎动物进化过程中,Caspase-1对气体皮质标的特异性发生了变化.
- 祖先的GSDMA被caspase-1激活,GSDMD后来在哺乳动物中扮演了这个角色.
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