Listeriolysin of Listeria monocytogenes forms Ca2+-permeable pores leading to intracellular Ca2+ oscillations
Listeriolysin of Listeria monocytogenes forms Ca2+-permeable pores leading to intracellular Ca2+ oscillations
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DOI：
10.1046/j.1462-5822.2002.00207.x
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发表时间：
2002-08-01
影响因子：
3.4
通讯作者：
Dreyer, F
中科院分区：
文献类型：
--
作者：
Repp, H;Pamukçi, Z;Dreyer, F
李斯特菌溶血素 (LLO) 是单核细胞增生李斯特菌的主要毒力因子，单核细胞增生李斯特菌是一种革兰氏阳性细菌，可导致危及生命的疾病。 LLO 通过未知机制触发各种信号事件和细胞效应，包括基因表达的调节。在这里，我们证明，在细胞外以亚溶解浓度应用 LLO 会导致人胚胎肾细胞的细胞内 Ca2+ 水平持久振荡；这是由于细胞外 Ca2+ 通过质膜中 LLO 形成的孔脉冲式流入所致。钙内流不需要内源性 Ca2+ 通道的活性。 LLO 形成的孔隙是瞬态的，并且在打开和关闭状态之间振荡。将细胞暴露于天然单核细胞增生李斯特菌后，还观察到孔形成和 Ca2+振荡。我们的数据表明，LLO 是单核细胞增生李斯特菌用来操纵细胞内 Ca2+ 水平的工具，而无需细菌与靶细胞直接接触。由于 Ca2+ 振荡调节细胞信号传导和基因表达，我们的研究结果为李斯特菌感染期间 LLO 诱导的广泛 Ca2+ 依赖性细胞反应提供了潜在的分子基础。
Listeriolysin (LLO) is a major virulence factor of Listeria monocytogenes , a Gram-positive bacterium that can cause life-threatening diseases. Various signalling events and cellular effects, including modulation of gene expression, are triggered by LLO through unknown mechanisms. Here, we demonstrate that LLO applied extracellularly at sublytic concentrations causes long-lasting oscillations of the intracellular Ca2+ level of human embryonic kidney cells; resulting from a pulsed influx of extracellular Ca2+ through pores that are formed by LLO in the plasma membrane. Calcium influx does not require the activity of endogenous Ca2+ channels. LLO-formed pores are transient and oscillate between open and closed states. Pore formation and Ca2+ oscillations were also observed after exposure of cells to native Listeria monocytogenes . Our data identify LLO as a tool used by Listeria monocytogenes to manipulate the intracellular Ca2+ level without direct contact of the bacterium with the target cell. As Ca2+ oscillations modulate cellular signalling and gene expression, our findings provide a potential molecular basis for the broad spectrum of Ca2+ -dependent cellular responses induced by LLO during Listeria infection.