修饰特异性蛋白质分泌的时空空间分析揭示了一个被itaconation激活的氨酸激酶
Wenjie Lu1,2,3,4,5, Yanling Zhang1,2,3,4,5, Xinrui Ni6,7
1The State Key Laboratory of Membrane Biology, Tsinghua University, Beijing, China.
Nature communications
|December 4, 2025
概括
这项研究引入了一种新的方法,PTM-based secretome profiling (PBSP),用于识别巨细胞中通过itaconation修饰的分泌蛋白质. PBSP揭示了这些修改如何影响细胞通信和免疫反应的新见解.
科学领域:
- 免疫学 免疫学 免疫学
- 蛋白质组学是指蛋白质组学.
- 细胞生物学 细胞生物学
背景情况:
- 巨细胞分泌信号蛋白,对免疫反应至关重要,由翻译后修饰 (PTMs) 调节.
- 伊塔可纳酸是巨细胞产生的代谢物,可以在细胞内诱导蛋白质的伊塔可纳化,但其细胞外作用尚不清楚.
- 了解细胞外PTM是解读细胞间通信的关键.
研究的目的:
- 开发和验证一种新的方法,用于分析PTM修饰蛋白质的分泌体.
- 为了研究 itaconation 对巨细胞分泌物的影响.
- 探索它对分泌蛋白质的功能影响.
主要方法:
- 开发了基于PTM的秘密基因组分析 (PBSP),使用生物对角探针进行活细胞标记.
- 集成的化学蛋白质工作流与基于spintip的亲和力净化 (FISAP) 和数据独立获取 (DIA) 质谱.
- 应用了PBSP来识别巨细胞分泌的 itaconated蛋白质.
主要成果:
- 鉴定了818种巨细胞分泌的化蛋白,其中447种是外体依赖的.
- 证明了FYN激酶的 itaconation 增强了其在巨细胞中的活性.
- 展示了PBSP的多功能性,通过分析烟酸诱导的化蛋白质.
结论:
- PBSP是一个强大的平台,用于发现PTM修饰的分泌蛋白质.
- 伊塔科纳显著影响巨细胞的分泌,并影响细胞信号传递.
- 这种方法为PTM在细胞间通信中的监管作用提供了新的见解.
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