Passive calcium leak via translocon is a first step for iPLA2-pathway regulated store operated channels activation.
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.
Flourakis
Matthieu
M
Laboratoire de Physiologie Cellulaire, INSERM U800, Bâtiment SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France. flourakismatt@yahoo.fr
Van Coppenolle
Fabien
F
Lehen'kyi
V'yacheslav
V
Beck
Benjamin
B
Skryma
Roman
R
Prevarskaya
Natalia
N
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004553:Electric Conductivity; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054522:Group VI Phospholipases A2; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D017136:Ion Transport; D018408:Patch-Clamp Techniques; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin / Q000494:pharmacology
D015220:Calcium Channels; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D004533:Egtazic Acid; D019284:Thapsigargin; D010741:Phospholipases A; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium