Pick Tillman, Beck Andreas, Gamayun Igor, Schwarz Yvonne, Schirra Claudia, Jung Martin, Krause Elmar, Niemeyer Barbara A, Zimmermann Richard, Lang Sven, Anken Eelco van, Cavalié Adolfo
Experimental and Clinical Pharmacology and Toxicology, Pre-clinical Center for Molecular Signalling (PZMS), Saarland University, 66421 Homburg, Germany.
Experimental and Clinical Pharmacology and Toxicology, Pre-clinical Center for Molecular Signalling (PZMS), Saarland University, 66421 Homburg, Germany.
Cell Calcium. 2021 Nov;99:102473. doi: 10.1016/j.ceca.2021.102473. Epub 2021 Sep 13.
The endoplasmic reticulum (ER) is extensively remodelled during the development of professional secretory cells to cope with high protein production. Since ER is the principal Ca store in the cell, we characterised the Ca homeostasis in NALM-6 and RPMI 8226 cells, which are commonly used as human pre-B and antibody secreting plasma cell models, respectively. Expression levels of Sec61 translocons and the corresponding Sec61-mediated Ca leak from ER, Ca storage capacity and store-operated Ca entry were significantly enlarged in the secretory RPMI 8226 cell line. Using an immunoglobulin M heavy chain producing HeLa cell model, we found that the enlarged Ca storage capacity and Ca leak from ER are linked to ER expansion. Our data delineates a developmental remodelling of Ca homeostasis in professional secretory cells in which a high Sec61-mediated Ca leak and, thus, a high Ca turnover in the ER is backed up by enhanced store-operated Ca entry.
在内分泌细胞发育过程中，内质网（ER）会发生广泛重塑以应对高蛋白产量。由于内质网是细胞内主要的钙库，我们对NALM-6细胞和RPMI 8226细胞中的钙稳态进行了表征，它们通常分别用作人前B细胞模型和抗体分泌浆细胞模型。分泌型RPMI 8226细胞系中，Sec61转运体的表达水平以及相应的Sec61介导的内质网钙泄漏、钙储存能力和储存式钙内流均显著增加。使用产生免疫球蛋白M重链的HeLa细胞模型，我们发现内质网钙储存能力的增加和钙泄漏与内质网扩张有关。我们的数据描绘了专职分泌细胞中钙稳态的发育重塑，其中Sec61介导的高钙泄漏以及因此内质网中的高钙周转率由增强的储存式钙内流支持。
