Passive calcium leak via translocon is a first step for iPLA2-pathway regulated store operated channels activation
Passive calcium leak via translocon is a first step for iPLA2-pathway regulated store operated channels activation
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DOI：
10.1096/fj.05-5254fje
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发表时间：
2006-06-01
期刊：
影响因子：
4.8
通讯作者：
Prevarskaya, Natalia
中科院分区：
文献类型：
--
作者：
Flourakis, Matthieu;Van Coppenolle, Fabien;Prevarskaya, Natalia
内质网 (ER) 内的钙浓度在细胞病理生理学中起着重要作用。导致内质网 Ca2+ 浓度最神秘的机制之一是被动钙泄漏。先前的研究表明易位子复合物对钙具有渗透性。然而，易位子参与被动钙渗漏尚未得到直接证明。此外，通过易位子被动储存消耗是否可以激活 SOC（储存操作通道）补充 ER 的问题仍然悬而未决。在这项研究中，我们首次证明毒胡萝卜素和钙螯合剂通过易位子消耗 ER。事实上，使用共聚焦成像，我们证明，当打开的易位子数量降低时，毒胡萝卜素和钙螯合剂都不会诱导内质网储备耗尽。我们还证明，通过易位子发生的钙泄漏会激活存储操作电流，从其动力学和药理学角度来看，这与毒胡萝卜素和 EGTA（但不是 IP3）引起的电流相似，从而强调了我们的假设，即通过易位子发生的钙泄漏是激活特定 iPLA2 调节的 SOC 的第一步。由于易位子存在于酵母和哺乳动物细胞中，我们的研究结果表明易位子相关的钙信号传导是一种常见现象。
Calcium concentration within the endoplasmic reticulum ( ER) plays an essential role in cell physiopathology. One of the most enigmatic mechanisms responsible for Ca2+ concentration in the ER is passive calcium leak. Previous studies have shown that the translocon complex is permeable to calcium. However, the involvement of the translocon in the passive calcium leak has not been directly demonstrated. Furthermore, the question whether the passive store depletion via the translocon could activate SOC ( store operated channels) replenishing the ER, remains still unresolved. In this study, for the first time, we show that thapsigargin and calcium chelators deplete ER via translocon. Indeed, using confocal imaging, we demonstrate that when the number of opened translocons was lowered neither thapsigargin nor calcium chelators could induce ER store depletion. We also demonstrate that calcium leakage occurring via the translocon activates store-operated current, which is, by its kinetic and pharmacology, similar to that evoked by thapsigargin and EGTA ( but not IP3), thus highlighting our hypothesis that calcium leakage via the translocon is a first step for activation of the specific iPLA2-regulated SOC. As the translocon is present in yeast and mammalian cells, our findings suggest that translocon-related calcium signaling is a common phenomenon.