Abstract
Depletion of intracellular calcium stores activates store-operated calcium entry across the plasma membrane in many cells. STIM1, the putative calcium sensor in the endoplasmic reticulum, and the calcium release-activated calcium (CRAC) modulator CRACM1 (also known as Orai1) in the plasma membrane have recently been shown to be essential for controlling the store-operated CRAC current (I(CRAC)). However, individual overexpression of either protein fails to significantly amplify I(CRAC). Here, we show that STIM1 and CRACM1 interact functionally. Overexpression of both proteins greatly potentiates I(CRAC), suggesting that STIM1 and CRACM1 mutually limit store-operated currents and that CRACM1 may be the long-sought CRAC channel.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Calcium / deficiency
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Calcium / metabolism
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Calcium Channels / drug effects
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Calcium Channels / metabolism*
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Calcium Signaling / drug effects
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Calcium Signaling / physiology*
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Cell Membrane / drug effects
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Cell Membrane / metabolism*
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Chelating Agents / pharmacology
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Endoplasmic Reticulum / drug effects
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Endoplasmic Reticulum / metabolism*
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Gene Expression / physiology
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Humans
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Inositol 1,4,5-Trisphosphate / pharmacology
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Intracellular Fluid / drug effects
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Intracellular Fluid / metabolism
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Jurkat Cells
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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ORAI1 Protein
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Stromal Interaction Molecule 1
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Up-Regulation / drug effects
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Up-Regulation / physiology
Substances
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Calcium Channels
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Chelating Agents
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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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STIM1 protein, human
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Stromal Interaction Molecule 1
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Inositol 1,4,5-Trisphosphate
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Calcium