在SARS-CoV-2中,尖端蛋白S1激活Cx43半通道,并扰乱细胞内Ca2+动态
Juan Prieto-Villalobos1, Claudia M Lucero2, Maximiliano Rovegno3
1Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile.
Biological research
|October 25, 2023
概括
SARS-CoV-2 尖端蛋白 S1 激活了连xin 43 (Cx43) 半通道,可能导致 COVID-19 细胞损伤. 针对这些半通道可能为2019年冠状病毒病提供新的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 病毒学 病毒学
- 疾病的分子机制.
背景情况:
- 冠状病毒疾病2019 (COVID-19) 是由SARS-CoV-2引起的.
- SARS-CoV-2 蛋白质对组织损伤的直接细胞效应尚未完全理解.
- 以前的研究将HIV gp120与增加的连接素43 (Cx43) 半通道活性联系起来.
研究的目的:
- 为了研究SARS-CoV-2尖端蛋白S1对Cx43半通道活性的影响.
- 要确定SARS-CoV-2 S1蛋白是否通过Cx43半通道直接影响细胞功能.
主要方法:
- 利用HeLa-Cx43细胞来评估Cx43半通道活动.
- 采用染料吸收实验来测量半通道开放.
- 执行补丁电生理学来分析单元电流.
- 测量ATP释放和细胞内动态.
主要成果:
- 根据SARS-CoV-2的S1蛋白峰剂量和时间的依赖性增加了Cx43半通道活性.
- 血管酶转化酶2 (ACE2) 的存在使这些效应变得更强大.
- 斯派克S1诱导的半通道开放导致ATP释放,并改变了细胞内信号传递.
结论:
- Cx43半通道是由SARS-CoV-2尖端S1蛋白激活的.
- 这些发现表明SARS-CoV-2诱导的细胞功能障碍的新机制.
- Cx43半通道代表了COVID-19及其长期影响的潜在治疗标.
相关概念视频
Feedback Regulation of Calcium Concentration
3.4K
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...
3.4K
Calmodulin-dependent Signaling
5.2K
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,...
5.2K
IP3/DAG Signaling Pathway
12.1K
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...
12.1K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
2.3K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
2.3K
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
G-Protein Gated Ion Channels
4.6K
GPCRs are primarily responsible for our sense of smell, taste, and vision. The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
Sensory...
4.6K


