在T细胞表面的Ca2+过渡体会在几秒钟的时间范围内触发快速的整合素激活
Yue Li1, ShiHui Wang1, YouHua Zhang2
1State Key Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.
Nature communications
|July 20, 2024
概括
快速的T细胞停止是通过在化学激素接触时细胞外度 ([Ca2+]ex) 迅速下降而实现的,前面是较慢的内外整合素激活. 这种机制确保了淋巴细胞的立即定位,并减少了皮肤炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 淋巴细胞定位依赖于快速的整合素激活,以立即停止.
- 化基因诱导的整合素激活通常是缓慢的,这对即时的细胞停止构成挑战.
研究的目的:
- 在化学激素刺激后,研究T细胞中快速整合素激活的机制.
- 确定细胞外在T细胞逮捕和回归中的作用.
主要方法:
- 测量了用CCL25刺激的T细胞中的细胞外度 ([Ca2+]ex) 变化.
- 利用塔林倒置来评估其在整合素激活中的作用.
- 阻止的流入,以评估其对T细胞滚动到停滞过渡和鼠标牛皮病模型中的回归的影响.
主要成果:
- CCL25触发了[Ca2+]ex的快速下降,在内外通路之前激活了αLβ2整合素.
- 塔林倒置影响了缓慢的整合素激活,但没有快速的依赖的激活.
- 阻断Ca2+的流入减少了T细胞的停止,导致皮肤病变,并缓解了牛皮的炎症.
结论:
- 细胞外的减少是αLβ2整合素激活的关键,快速触发,确保立即的T细胞停止.
- 这种机制补充了缓慢的内外激活,优化了淋巴细胞向炎症部位的指导.
- 针对这种依赖的途径可能为炎症性皮肤疾病提供治疗策略.
相关概念视频
Activation of Integrins
3.4K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.4K
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
Integrins
3.9K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
3.9K
Diversity in Cell Signaling Responses
6.4K
The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity.
Graded and Abrupt Responses
Some signaling systems generate...
Graded and Abrupt Responses
Some signaling systems generate...
6.4K
T Cell Activation and Clonal Selection
696
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
696
Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K


