Remodelling of Ca2+ homeostasis is linked to enlarged endoplasmic reticulum in secretory cells

Abstract

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 Ca²⁺ store in the cell, we characterised the Ca²⁺ 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 Ca²⁺ leak from ER, Ca²⁺ storage capacity and store-operated Ca²⁺ 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 Ca²⁺ storage capacity and Ca²⁺ leak from ER are linked to ER expansion. Our data delineates a developmental remodelling of Ca²⁺ homeostasis in professional secretory cells in which a high Sec61-mediated Ca²⁺ leak and, thus, a high Ca²⁺ turnover in the ER is backed up by enhanced store-operated Ca²⁺ entry.

Keywords: Ca2+ homeostasis; Ca2+ leak; ER expansion; Sec61 translocon; Secretory cells; Store-operated calcium entry.