Sec61 complexes form ubiquitous ER Ca2+ leak channels

Abstract

In mammalian cells, the endoplasmic reticulum (ER) plays a key role in protein biogenesis and in calcium signalling. The heterotrimeric Sec61 complex in the ER membrane provides an aqueous pathway for transporting newly synthesized polypeptides into the ER lumen and may also allow calcium leakage from the ER into the cytosol. In this study, planar lipid bilayer experiments demonstrated that the Sec61 complex is permeable to calcium ions. We also investigated whether silencing the SEC61A1 gene affected calcium leakage from the ER. Silencing the SEC61A1 gene using two different siRNAs in HeLa cells for 96 hours had little effect on cell growth and viability. However, calcium leakage from the ER was greatly decreased in the SEC61A1-silenced cells. Thus, the Sec61 complexes that are present in the ER membrane of nucleated cells form calcium leak channels that may play a crucial role in calcium homeostasis.