丹特病1-链接的新型CLCN5突变导致异常位置和减少的离子电流
Yan Wang1, Lizhen Xu2, Ying Zhang3
1Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
International journal of biological macromolecules
|December 7, 2023
概括
两个新的CLCN5突变导致Dent病1 (DD1),一种罕见的脏疾病. 这些突变破坏了化物通道5 (ClC-5) 功能,导致细胞损伤和细胞行为改变,为疾病机制提供了洞察力.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 腎臟病學 (nephrology) 是一種醫學專業.
背景情况:
- 丹特病是一种罕见的X连接管脏疾病.
- 它的特征是低分子量蛋白尿,高尿和骨.
- CLCN5中的突变会导致丹特病1 (DD1),但机制尚不清楚.
研究的目的:
- 在Dent病1患者中识别新的CLCN5突变.
- 阐明这些突变的病理生理机制.
- 研究CLCN5功能障碍的细胞后果.
主要方法:
- 整体外基因组测序和生物信息学分析.
- ClC-5同质模型的分子动力学模拟.
- 在HK-2细胞中CLCN5变体的体外过度表达,包括亚细胞局部化,聚合物形成,离子运输,细胞粘附,迁移,内细胞检测和转录基因分析.
主要成果:
- 发现了两个新的CLCN5突变 (c.749G>A,p.G250D和c.829A>C,p.T277P).
- 模拟表明突变会破坏ClC-5结构的稳定.
- 过度表达导致ER错位,聚合,破坏离子运输,改变细胞功能和显著的转录基因变化,其中G250D显示出更强的效应.
结论:
- 已识别的CLCN5突变在Dent病1中具有病原性.
- 干扰的ClC-5功能和细胞变化导致DD1中的功能障碍.
- 这些发现表明了Dent病的潜在诊断生物标志物和治疗点.
相关概念视频
Notch Signaling Pathway
4.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K
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
Ligand-gated Ion Channels
12.4K
Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
12.4K
Voltage-gated Ion Channels
8.2K
Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
8.2K
Cadherins in Tissue Organization
3.0K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
3.0K
Non-gated Ion Channels
6.8K
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....
6.8K


