title: Modulation of STIM1 and capacitative Ca2+ entry by the endoplasmic reticulum luminal oxidoreductase ERp57.
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.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Prins
authors.forename: Jody
authors.initials: J
authors.lastname: Groenendyk
authors.forename: Nicolas
authors.initials: N
authors.lastname: Touret
authors.forename: Marek
authors.initials: M
authors.lastname: Michalak
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D020013:Calcium Signaling; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D031541:Fluorescence Resonance Energy Transfer; D055785:Gene Knockdown Techniques; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases / Q000172:deficiency / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D000071737:Stromal Interaction Molecule 1; D013329:Structure-Activity Relationship
chemical_list: D015220:Calcium Channels; D004220:Disulfides; D008562:Membrane Glycoproteins; D050505:Mutant Proteins; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; D003545:Cysteine; D002118:Calcium