Stanniocalcin 2 is a negative modulator of store-operated calcium entry

William Zeiger, Daisuke Ito, Carol Swetlik, Masatsugu Oh-hora, Mitchel L. Villereal, Gopal Thinakaran

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The regulation of cellular Ca 2+ homeostasis is essential for innumerable physiological and pathological processes. Stanniocalcin 1, a secreted glycoprotein hormone originally described in fish, is a well-established endocrine regulator of gill Ca 2+ uptake during hypercalcemia. While there are two mammalian Stanniocalcin homologs (STC1 and STC2), their precise molecular functions remain unknown. Notably, STC2 is a prosurvival component of the unfolded protein response. Here, we demonstrate a cell-intrinsic role for STC2 in the regulation of store-operated Ca 2+ entry (SOCE). Fibroblasts cultured from Stc2 knockout mice accumulate higher levels of cytosolic Ca 2+ following endoplasmic reticulum (ER) Ca 2+ store depletion, specifically due to an increase in extracellular Ca 2+ influx through store-operated Ca 2+ channels (SOC). The knockdown of STC2 expression in a hippocampal cell line also potentiates SOCE, and the overexpression of STC2 attenuates SOCE. Moreover, STC2 interacts with the ER Ca 2+ sensor STIM1, which activates SOCs following ER store depletion. These results define a novel molecular function for STC2 as a negative modulator of SOCE and provide the first direct evidence for the regulation of Ca 2+ homeostasis by mammalian STC2. Furthermore, our findings implicate the modulation of SOCE through STC2 expression as one of the prosurvival measures of the unfolded protein response.

Original languageEnglish
Pages (from-to)3710-3722
Number of pages13
JournalMolecular and Cellular Biology
Volume31
Issue number18
DOIs
Publication statusPublished - 2011 Sep

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Endoplasmic Reticulum
Unfolded Protein Response
Calcium
Homeostasis
Physiological Phenomena
Hypercalcemia
Pathologic Processes
Knockout Mice
Glycoproteins
Fishes
Fibroblasts
Hormones
Cell Line
teleocalcin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Zeiger, W., Ito, D., Swetlik, C., Oh-hora, M., Villereal, M. L., & Thinakaran, G. (2011). Stanniocalcin 2 is a negative modulator of store-operated calcium entry. Molecular and Cellular Biology, 31(18), 3710-3722. https://doi.org/10.1128/MCB.05140-11

Stanniocalcin 2 is a negative modulator of store-operated calcium entry. / Zeiger, William; Ito, Daisuke; Swetlik, Carol; Oh-hora, Masatsugu; Villereal, Mitchel L.; Thinakaran, Gopal.

In: Molecular and Cellular Biology, Vol. 31, No. 18, 09.2011, p. 3710-3722.

Research output: Contribution to journalArticle

Zeiger, W, Ito, D, Swetlik, C, Oh-hora, M, Villereal, ML & Thinakaran, G 2011, 'Stanniocalcin 2 is a negative modulator of store-operated calcium entry', Molecular and Cellular Biology, vol. 31, no. 18, pp. 3710-3722. https://doi.org/10.1128/MCB.05140-11
Zeiger, William ; Ito, Daisuke ; Swetlik, Carol ; Oh-hora, Masatsugu ; Villereal, Mitchel L. ; Thinakaran, Gopal. / Stanniocalcin 2 is a negative modulator of store-operated calcium entry. In: Molecular and Cellular Biology. 2011 ; Vol. 31, No. 18. pp. 3710-3722.
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