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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Calcium / metabolism*
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Calcium Channels / metabolism
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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Cell Membrane / metabolism*
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Cells, Cultured
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Cytosol / metabolism*
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Endoplasmic Reticulum / metabolism*
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Feedback, Physiological
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HeLa Cells
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Humans
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Ion Channel Gating
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Microscopy, Fluorescence
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Neoplasm Proteins / metabolism
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ORAI1 Protein
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Protein Transport
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RNA Interference
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RNA, Small Interfering / metabolism
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Recombinant Fusion Proteins / metabolism
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Stromal Interaction Molecule 1
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Stromal Interaction Molecule 2
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Time Factors
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Transfection
Substances
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Calcium Channels
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Cell Adhesion Molecules
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Membrane Proteins
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Neoplasm Proteins
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ORAI1 Protein
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ORAI1 protein, human
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RNA, Small Interfering
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Recombinant Fusion Proteins
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STIM1 protein, human
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STIM2 protein, human
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Stromal Interaction Molecule 1
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Stromal Interaction Molecule 2
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Calcium