ABCG2 是一个 itaconate 出口商,通过减轻 TFEB 依赖的 lysosomal 生物生成来限制抗菌天生的免疫力
Chao Chen1, Zhenxing Zhang1, Caiyun Liu2
1Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Cell metabolism
|January 5, 2024
概括
伊塔科纳酸通过ABCG2输送器离开巨细胞. 阻止这种出口可以增强 lysosomal biogenesis 和抗菌免疫力,这表明对细菌感染的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
背景情况:
- 伊塔科纳酸是巨细胞中产生的关键代谢物,具有已知的调节功能.
- 目前,从巨细胞向细胞外空间出口伊塔科纳酸的机制尚不清楚.
- 了解伊塔康酸运输对于阐明它在天生的免疫力中的作用至关重要.
研究的目的:
- 为了确定负责从巨细胞中输出伊塔科纳特的分子机制.
- 调查受损伊塔康酸盐出口对巨细胞生物学和免疫的功能后果.
- 探索针对细菌感染的伊塔科纳酸出口的治疗潜力.
主要方法:
- 在人类和小鼠巨细胞中进行基因查,以确定伊塔科纳特出口机制.
- 使用ATPase测定来确认运输机制.
- 使用沙门氏菌Typhimurium感染的小鼠模型来评估体内疗效.
主要成果:
- 鉴定出ATP结合盒载体G2 (ABCG2) 是通过依赖ATPase的方式将伊塔科纳酸从细胞质输出到细胞外空间的输出者.
- 缺乏ABCG2介导伊塔康酸出口的巨体表现出增强的转录因子TFEB依赖的溶酶体生物发生.
- 在巨细胞中ABCG2介导的伊塔科纳特出口的缺陷增强了抗菌天生的免疫防御,正如Salmonella Typhimurium感染模型所示.
结论:
- 经ABCG2介导的伊塔科纳酸出口是一种关键的调控途径,限制了TFEB依赖的溶酶体生物发生和抗菌天生的免疫在炎症性巨细胞中.
- 抑制ABCG2介导的伊塔康酸出口是一种通过增强宿主防御机制来治疗细菌感染的潜在治疗策略.
更多相关视频
08:32Assessment of Intestinal Transcytosis of Neonatal Escherichia coli Bacteremia Isolates
Published on: February 17, 2023
1.3K
11:21Forward Genetics Screens Using Macrophages to Identify Toxoplasma gondii Genes Important for Resistance to IFN-γ-Dependent Cell Autonomous Immunity
Published on: March 12, 2015
11.1K
相关概念视频
01:27ABC Transporters: Importer
2.7K
ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
2.7K
01:31ABC Transporters: Exporter
4.3K
ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
4.3K
01:15Transcytosis of IgG
2.8K
Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
2.8K
01:31Defense Against Bacterial Pathogens
1.4K
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
1.4K
01:09GPCRs Regulate Adenylyl Cylase Activity
5.6K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.6K