质子选择性导电性和溶酶体阴离子通道TMEM175的门
Tobias Schulze1,2, Timon Sprave1, Carolin Groebe1,3
1Department of Biology, Membrane Biophysics, Technical University of Darmstadt, Darmstadt 64287, Germany.
概括
lysosomal 道 TMEM1755 是一个
科学领域:
- 细胞生物学 细胞生物学
- 离子通道生理学 离子通道生理学
- 分子神经科学 分子神经科学
背景情况:
- lysosomal 阴离子通道 TMEM175 对于 pH 稳态和 lysosome 功能至关重要.
- 异常的TMEM175活性与帕金森病的病原发生有关.
- TMEM175表现出显著的质子 (H+) 透性,挑战其最初的描述为K+选择性.
研究的目的:
- 为了研究人类TMEM175电导率和离子性质的复杂变化,以应对光线pH值的变化.
- 阐明TMEM175的质子透性背后的机制及其在溶酶体生理学中的作用.
主要方法:
- 电生理学记录 (全细胞和溶酶体) 用于分析TMEM175电流和逆转潜力.
- 分子动力学模拟以确定TMEM175通道内的关键残留物和相互作用.
- 位点定向突变发生 (H57Y) 来评估特定残留物的功能影响.
主要成果:
- 光线pH的降低 (7.4至4.7) 显著增加了TMEM175电流,并将逆转潜力转向H+平衡.
- 分子动力学模拟确定H57是参与盐桥形成的关键残留物.
- TMEM175 H57Y突变体显示H+和K+电导率降低和选择性改变.
结论:
- TMEM175介导的H+流可以快速消散溶酶体pH梯度.
- 特定的残留物,如H57,对于TMEM175的离子导电性和选择性至关重要.
- 了解TMEM175的电生理学提供了对溶酶体功能和帕金森病的见解.
相关概念视频
Non-gated Ion Channels
8.0K
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....
8.0K
Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.8K
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...
3.8K
Mechanically-gated Ion Channels
7.6K
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
7.6K
Ion Channels
91.1K
The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
91.1K
ATP Driven Pumps III: V-type Pumps
4.6K
V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V1Vo-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
4.6K
Protein Transport into the Inner Mitochondrial Membrane
4.8K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
4.8K


