Abstract
STIM1 is an endoplasmic reticulum (ER) membrane Ca(2+) sensor responsible for activation of store-operated Ca(2+) influx. We discovered that STIM1 oligomerization and store-operated Ca(2+) entry (SOC) are modulated by the ER oxidoreductase ERp57. ERp57 interacts with the ER luminal domain of STIM1, with this interaction involving two conserved cysteine residues, C(49) and C(56). SOC is accelerated in the absence of ERp57 and inhibited in C(49) and C(56) mutants of STIM1. We show that ERp57, by ER luminal interaction with STIM1, has a modulatory role in capacitative Ca(2+) entry. This is the first demonstration of a protein involved in ER intraluminal regulation of STIM1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism*
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Calcium Channels
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Calcium Signaling*
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Cysteine / metabolism
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Disulfides / metabolism
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Endoplasmic Reticulum / enzymology*
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Fluorescence Resonance Energy Transfer
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Gene Knockdown Techniques
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / metabolism*
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Mice
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Mutant Proteins / chemistry
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Mutant Proteins / metabolism
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Protein Binding
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Protein Disulfide-Isomerases / deficiency
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Protein Disulfide-Isomerases / metabolism*
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Protein Structure, Tertiary
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Stromal Interaction Molecule 1
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Structure-Activity Relationship
Substances
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Calcium Channels
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Disulfides
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Membrane Glycoproteins
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Mutant Proteins
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Stim1 protein, mouse
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Stromal Interaction Molecule 1
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Pdia3 protein, mouse
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Protein Disulfide-Isomerases
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Cysteine
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Calcium