天生的免疫力信号来自戈尔吉.
1Graduate School of Life Sciences, Tohoku University, Sendai, Japan. tomohiko.taguchi.b8@tohoku.ac.jp.
Sub-cellular biochemistry
|February 20, 2026
概括
循环GMP-AMP合成酶 (cGAS) 刺激干扰素基因 (STING) 途径驱动炎症. STING激活涉及ER-to-Golgi运输,与COPA综合征相关的失调.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- cGAS-STING通路是先天免疫的关键调节者,感知细胞质双链DNA (dsDNA) 来启动炎症反应.
- 激活涉及STING从内分泌网膜 (ER) 到戈尔吉装置的转位,导致通过TBK1和IRF3.3产生I型干扰素.
- 在ER和Golgi之间失调的膜贩运与COPA综合征等自身炎症性疾病有关.
研究的目的:
- 通过膜贩运动态探索cGAS-STING通路激活的调节.
- 阐明控制跨戈尔吉网络 (TGN) TBK1/IRF3激活的分子机制.
主要方法:
- 使用活细胞成像研究STING局部化和动态.
- 在TGN分析蛋白质与蛋白质相互作用.
- 利用COPA综合征的遗传模型研究ER-Golgi传输缺陷.
主要成果:
- 从ER转移到戈尔吉河的STING转移对于其激活至关重要.
- 在TGN的特定膜贩运事件对于TBK1/IRF3的招募和激活至关重要.
- 影响ER-Golgi传输的突变破坏了STING信号,并导致自身炎症.
结论:
- 在ER和Golgi之间的膜交通是cGAS-STING通道的关键监管检查点.
- 针对STING介导的信号传递和相关的膜贩运通路,对于炎症性疾病和癌症具有治疗潜力.
相关概念视频
IP3/DAG Signaling Pathway
15.2K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
15.2K
Golgi Matrix Proteins
2.5K
Golgi matrix proteins are a group of highly dynamic proteins that maintain the stacked structure of Golgi. These proteins adapt to rapid morphological changes of the Golgi during the cell cycle. During cell division, mild proteolysis removes these connections resulting in Golgi unstacking. In The daughter cells, these proteins help reassemble the unstacked Golgi.
One of the first identified Golgi matrix proteins was GM130, a rod-like protein located in the cis-Golgi. Subsequently, many Golgi...
One of the first identified Golgi matrix proteins was GM130, a rod-like protein located in the cis-Golgi. Subsequently, many Golgi...
2.5K
GPI Anchoring of Proteins in the ER Membrane
5.6K
GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
5.6K
Intracellular Signaling Cascades
53.9K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
53.9K
Transport Across the Golgi
6.3K
While it is unclear how molecules move between adjacent Golgi cisternae, it is apparent that the molecules move from cis- cisterna, the entry face, to the trans- cisterna, the exit face. Experiments initially suggested vesicles that bud from one cisterna and fuse with the next cisterna to transport proteins between the cisternae. This vesicular transport model describes the Golgi apparatus as a relatively static structure with a unique enzyme composition in each cisterna. Molecules are...
6.3K
What are Second Messengers?
91.1K
Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
91.1K


