STIM2 Is a Feedback Regulator that Stabilizes Basal Cytosolic and Endoplasmic Reticulum Ca2+ Levels

Onn Brandman, Jen Liou, Wei Sun Park, Tobias Meyer

Research output: Contribution to journalArticle

484 Scopus citations

Abstract

Deviations in basal Ca2+ levels interfere with receptor-mediated Ca2+ signaling as well as endoplasmic reticulum (ER) and mitochondrial function. While defective basal Ca2+ regulation has been linked to various diseases, the regulatory mechanism that controls basal Ca2+ is poorly understood. Here we performed an siRNA screen of the human signaling proteome to identify regulators of basal Ca2+ concentration and found STIM2 as the strongest positive regulator. In contrast to STIM1, a recently discovered signal transducer that triggers Ca2+ influx in response to receptor-mediated depletion of ER Ca2+ stores, STIM2 activated Ca2+ influx upon smaller decreases in ER Ca2+. STIM2, like STIM1, caused Ca2+ influx via activation of the plasma membrane Ca2+ channel Orai1. Our study places STIM2 at the center of a feedback module that keeps basal cytosolic and ER Ca2+ concentrations within tight limits.

Original languageEnglish (US)
Pages (from-to)1327-1339
Number of pages13
JournalCell
Volume131
Issue number7
DOIs
StatePublished - Dec 28 2007

Keywords

  • CELLBIO
  • SIGNALING

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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