Helicobacter pylori vacuolating toxin forms anion-selective channels in planar lipid bilayers: possible implications for the mechanism of cellular vacuolation.
Helicobacter pylori vacuolating toxin forms anion-selective channels in planar lipid bilayers: possible implications for the mechanism of cellular vacuolation.
复制标题
幽门螺杆菌空泡毒素在平面脂质双层中形成阴离子选择性通道：对细胞空泡形成机制的可能影响。
DOI：
10.1016/s0006-3495(99)77301-7
复制
发表时间：
1999
影响因子：
3.4
通讯作者：
M. Zoratti
中科院分区：
文献类型：
--
作者：
F. Tombola;Cristina Carlesso;I. Szabó;M. Bernard;J. Reyrat;J. Telford;R. Rappuoli;C. Montecucco;E. Papini;M. Zoratti
幽门螺杆菌VacA毒素在与该细菌相关的胃部病理中起主要作用。当添加到培养的细胞中时，VacA会诱导空泡化，这种影响因预先将毒素暴露在低pH值下而增强。其作用机制尚不清楚。我们在这里报道，VacA在人工膜中形成阴离子选择性的、电压依赖的孔。酸性条件或低pH条件下VacA的预处理能极大地促进通道的形成。没有确定对特定脂肪的需求(S)。选择性研究表明，阴离子选择性在pH值为4.8-12的范围内保持不变，渗透性顺序如下：Cl−≈HCO3−>；pyruvate>；gluconate>；K+≈Li+≈Ba2+>；NH4+.膜通透性是由于在10-30ps(2MKCl2)范围内加入了具有电压依赖电导的通道，表现出电压无关的高开放概率。NH2末端结构域(P37)的缺失或VacA的化学修饰可抑制HeLa细胞的通道活性和空泡化，但不影响细胞对毒素的内化。总之，这些观察结果强烈表明，VacA通道的形成是诱导细胞空泡化所必需的，可能是通过诱导细胞内酸性隔间的渗透失衡来实现的。
TheHelicobacter pyloriVacA toxin plays a major role in the gastric pathologies associated with this bacterium. When added to cultured cells, VacA induces vacuolation, an effect potentiated by preexposure of the toxin to low pH. Its mechanism of action is unknown. We report here that VacA forms anion-selective, voltage-dependent pores in artificial membranes. Channel formation was greatly potentiated by acidic conditions or by pretreatment of VacA at low pH. No requirement for particular lipid(s) was identified. Selectivity studies showed that anion selectivity was maintained over the pH range 4.8–12, with the following permeability sequence: Cl−≈HCO3−>pyruvate>gluconate>K+≈Li+≈Ba2+>NH4+. Membrane permeabilization was due to the incorporation of channels with a voltage-dependent conductance in the 10–30 pS range (2M KCl), displaying a voltage-independent high open probability. Deletion of the NH2terminus domain (p37) or chemical modification of VacA by diethylpyrocarbonate inhibited both channel activity and vacuolation of HeLa cells without affecting toxin internalization by the cells. Collectively, these observations strongly suggest that VacA channel formation is needed to induce cellular vacuolation, possibly by inducing an osmotic imbalance of intracellular acidic compartments.
登录
查看更多内容
阴离子抑制大鼠肝脏多泡体中的质子泵。
DOI：
--
发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
VanDyke,RW
通讯作者：
VanDyke,RW
DOI：
10.1073/pnas.80.11.3334
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
GALLOWAY, CJ;DEAN, GE;MELLMAN, I
通讯作者：
MELLMAN, I
影响因子：
158.5
作者：
PARSONNET, J;HANSEN, S;FRIEDMAN, GD
通讯作者：
FRIEDMAN, GD
莫能菌素诱导的 H-2 肝癌细胞高尔基体池肿胀的动力学。
影响因子：
6.6
作者：
Morre,DJ;Minnifield,N;Mollenhauer,HH
通讯作者：
Mollenhauer,HH