Medical Biochemistry and Molecular Biology, Saarland University, Homburg, Germany.
Channels (Austin). 2011 May-Jun;5(3):228-35. doi: 10.4161/chan.5.3.15314. Epub 2011 May 1.
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.
在哺乳动物细胞中，内质网 (ER) 在蛋白质生物发生和钙信号传导中发挥着关键作用。ER 膜中的异三聚体 Sec61 复合物为将新合成的多肽转运到 ER 腔中提供了一个水相途径，并且还可能允许钙从 ER 渗漏到细胞质中。在这项研究中，平面脂质双层实验表明 Sec61 复合物可渗透钙离子。我们还研究了沉默 SEC61A1 基因是否会影响 ER 中的钙渗漏。用两种不同的 siRNA 在 HeLa 细胞中沉默 SEC61A1 基因 96 小时对细胞生长和活力几乎没有影响。然而，在 SEC61A1 沉默的细胞中，从 ER 中漏出的钙大大减少。因此，存在于有核细胞 ER 膜中的 Sec61 复合物形成钙泄漏通道，这些通道可能在钙稳态中发挥关键作用。
