title: Store-operated Ca2+ entry is sensitive to the extracellular Ca2+ concentration through plasma membrane STIM1.
abstract: Store-operated Ca(2+) entry (SOCE) is a major mechanism for Ca(2+) influx in platelets and other cells activated by a reduction in Ca(2+) concentration in the intracellular stores. SOCE has been reported to be regulated by extracellular Ca(2+), although the underlying mechanism remains unclear. Here we have examined the involvement of plasma membrane-located STIM1 (PM-STIM1) in the regulation of SOCE by extracellular Ca(2+). Treatment of platelets with the SERCA inhibitor thapsigargin (TG) induced Mn(2+) entry, which was inhibited by extracellular Ca(2+) in a concentration-dependent manner. Incubation of platelets with a specific antibody, which recognizes the extracellular amino acid sequence 25-139 of PM-STIM1 that contains the Ca(2+)-binding domain, prevented the inactivation of Ca(2+) entry induced by extracellular Ca(2+). TG induced translocation of STIM1 to the plasma membrane (PM), an event that was found to be Ca(2+)-dependent. In addition, TG stimulated association of PM-STIM1 with Orai1, an event that was not prevented by stabilization of the membrane cytoskeleton using jasplakinolide. These findings suggest that PM-STIM1 is important for the inactivation of SOCE by extracellular Ca(2+), an event that is likely to be mediated by interaction with Orai1.
authors.affiliation: Department of Physiology (Cellular Physiology Research Group), University of Extremadura, 10071 Cáceres, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Jardín
authors.forename: José J
authors.initials: JJ
authors.lastname: López
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Redondo
authors.forename: Ginés M
authors.initials: GM
authors.lastname: Salido
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rosado
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000097:blood; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008345:Manganese / Q000378:metabolism; D008565:Membrane Proteins / Q000097:blood*; D009363:Neoplasm Proteins / Q000097:blood*; D000071740:ORAI1 Protein; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000097:blood; D000071737:Stromal Interaction Molecule 1; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D008345:Manganese; D019284:Thapsigargin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium