蛋白分离酶VCP/p97通过调节SYK激活促进宿主抗真菌防御
Zhugui Shao1,2,3, Li Wang3,4, Limin Cao3
1Key Laboratory of Infection and Immunity of Shandong Province & Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong, P. R. China.
PLoS pathogens
|October 29, 2024
概括
含有瓦洛辛的蛋白质 (VCP) 是Dectin-1免疫反应中新发现的信号传感器. VCP 调节 SYK 激活,对宿主防御抗 Candida albicans 等真菌感染至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
背景情况:
- C型乳素受体 (CLR) 对于抗真菌免疫至关重要.
- 关于CLR信号传递的分子机制,特别是Dectin-1,需要进一步阐明.
研究的目的:
- 识别参与Dectin-1信号传递的新型氨酸酸化蛋白质.
- 调查瓦洛辛含蛋白 (VCP) /p97在Dectin-1-介导免疫反应中的作用.
主要方法:
- 在骨髓衍生的巨细胞 (BMDMs) 和树突细胞 (BMDCs) 中利用了VCP的淘汰和化学抑制.
- 进行生物化学分析以评估蛋白质复合体形成 (VCP,UFD1,SYK,SHP-1) 和无处不在.
- 在Candida albicans感染模型中使用基因剥离和药理抑制在体内研究VCP的作用.
主要成果:
- 降低/抑制VCP损害了德克丁-1诱导的SYK激活和促炎性细胞因子 (TNF-α,IL-6,CXCL1) 的产生.
- VCP和UFD1与SYK和SHP-1形成一个复合体,VCP通过ubiquitination促进SHP-1的降解.
- 在中性粒细胞/巨细胞中缺乏VCP的小鼠对Candida albicans感染的易感性增加.
结论:
- 含有瓦洛辛的蛋白质 (VCP) 是Dectin-1通路中的一个关键的,以前未被识别的信号转换器.
- VCP通过促进酸酶SHP-1的降解来调节SYK的激活.
- VCP在对抗真菌病原体的宿主防御中发挥着重要作用,并代表着潜在的治疗点.
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