RabGAP1L调节Rab7A和Rab10,以协调细胞自主免疫
Atsuko Minowa-Nozawa1, Takashi Nozawa1, Kazunori Murase1
1Department of Microbiology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Cell reports
|April 17, 2025
概括
拉布GTPase激活蛋白1-like (RabGAP1L) 通过控制细菌感染期间的Rab GTPases来调节细胞自主免疫. 这种蛋白调节选择性自和细菌驱逐,有助于病原体的消除.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 细胞自主免疫采用膜贩运,包括选择性自和细胞外驱逐,以对抗细胞内病原体.
- 协调这些独特的细胞自主防御系统的调节机制在很大程度上仍然未被描述.
研究的目的:
- 调查Rab GTPase激活蛋白1-like (RabGAP1L) 在调节细胞自主免疫反应对抗A型 estreptococcus (GAS) 的作用.
- 阐明在感染期间由RabGAP1L调节的特定Rab GTPases和细胞通路.
主要方法:
- 使用共聚焦显微镜分析Rab GTPases的局部和功能以及贩运途径.
- 基因操纵,包括ATG7和ATG5淘汰模式,用于评估自缺陷的影响.
- 用A组链球菌 (GAS) 的感染模型来研究宿主-病原体相互作用.
主要成果:
- RabGAP1L 禁用 Rab7A 和 Rab10,它们是细胞防御机制的关键调节者.
- Rab7A通过促进内分泌体贩运来促进针对GAS的选择性自.
- Rab7A和Rab10通过干扰Rab11A阳性循环内分泌体形成来抑制GAS驱逐,而自缺陷细胞显示出增加的RabGAP1L依赖细菌驱逐.
结论:
- RabGAP1L通过协调涉及Rab GTPases的不同途径,充当细胞自主免疫的关键调节者.
- 这些发现揭示了一个新的机制,RabGAP1L平衡了选择性自和细菌驱逐,以增强细胞内病原体清除.
相关概念视频
01:14Rab Proteins
3.8K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
3.8K
01:25Rab Cascades
2.6K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.6K
01:24Small GTPases - Ras and Rho
3.8K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
3.8K
02:38The Ras Gene
6.1K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
Ras is a...
6.1K
01:33Coat Assembly and GTPases
3.4K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.4K
02:14GTPases and their Regulation
8.1K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
8.1K