SERCA调节器揭示了T淋巴细胞Ca2+存储的独特信号和功能作用
Md Nasim Uddin1, David W Thomas1
1Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy University of the Pacific, Stockton, CA 95211, USA.
International journal of molecular sciences
|November 27, 2024
概括
塞尔卡激活剂CDN1163对T淋巴细胞 (Ca2+) 储存有复杂的影响. 短期使用会抑制Ca2+的吸收,而长期使用会改变Ca2+的释放,并保护细胞免受某些抑制剂的影响.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase (SERCA) 激活剂是新兴的药理学工具. 这些激活剂的作用非常广泛.
- CDN1163是一种新型全性SERCA激活剂.
- 了解它对T淋巴细胞信号传递的影响至关重要.
研究的目的:
- 为了研究CDN1163对Jurkat T淋巴细胞中 (Ca2+) 储量的影响.
- 确定CDN1163在SERCA 2b和SERCA 3上的异型特异性作用.
- 检查CDN1163.3的时间依赖和度依赖的影响.
主要方法:
- 利用Jurkat T淋巴细胞作为Ca2+信号传递的模型系统.
- 已建立的低剂量SERCA抑制剂方案 (thapsigargin和tBHQ) 来区分SERCA 2b和SERCA 3储存.
- 在短期 (0-30分钟) 和长期 (>12小时) CDN1163暴露后评估的Ca2+释放和吸收动态.
主要成果:
- 短期的CDN1163暴露抑制了Ca2+的吸收,并减少了来自SERCA 2b储存的Ca2+释放.
- 短期CDN1163在SERCA 3储存器上表现出SERCA激活作用,增加了Ca2+的释放.
- 长期的CDN1163暴露逆转了这些效应,增加了来自SERCA 2b的Ca2+释放,并减少了来自SERCA 3的储存,从而提供了对thapsigargin诱导的生长抑制的保护.
结论:
- CDN1163表现出复杂的,时间敏感的,以及SERCA异形特异性的T淋巴细胞Ca2+储存的调节.
- 该化合物的效应在短期和长期暴露之间存在显著差异.
- 长期的CDN1163治疗重塑Ca2+储量,并影响T淋巴细胞活力.
相关概念视频
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
Feedback Regulation of Calcium Concentration
3.3K
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.3K
T Cell Activation and Clonal Selection
669
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...
669
T Cell Types and Functions
954
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
954
B Cell Activation and Differentiation
1.6K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.6K
Amplifying Signals via Second Messengers
6.8K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
6.8K


