Flourakis Matthieu, Van Coppenolle Fabien, Lehen'kyi V'yacheslav, Beck Benjamin, Skryma Roman, Prevarskaya Natalia
Laboratoire de Physiologie Cellulaire, INSERM U800, Bâtiment SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France.
FASEB J. 2006 Jun;20(8):1215-7. doi: 10.1096/fj.05-5254fje. Epub 2006 Apr 12.
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.
内质网（ER）内的钙浓度在细胞生理病理学中起着至关重要的作用。导致内质网中Ca2+浓度变化的最神秘机制之一是被动钙泄漏。先前的研究表明，转运体复合物对钙具有通透性。然而，转运体在被动钙泄漏中的作用尚未得到直接证实。此外，通过转运体导致的内质网钙库被动耗竭是否能够激活补充内质网钙库的储存操纵性通道（SOC）这一问题仍未得到解决。在本研究中，我们首次表明，毒胡萝卜素和钙螯合剂可通过转运体耗尽内质网中的钙。事实上，利用共聚焦成像技术，我们证明当开放的转运体数量减少时，毒胡萝卜素和钙螯合剂均无法诱导内质网钙库耗竭。我们还证明，通过转运体发生的钙泄漏可激活储存操纵性电流，从动力学和药理学角度来看，该电流与毒胡萝卜素和乙二醇双四乙酸（EGTA，而非肌醇三磷酸）所诱发的电流相似，从而突出了我们的假设，即通过转运体的钙泄漏是激活特定的由iPLA2调节的SOC的第一步。由于转运体存在于酵母和哺乳动物细胞中，我们的研究结果表明，与转运体相关的钙信号传导是一种常见现象。
