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Science China Life Sciences

, Volume 58, Issue 1, pp 48–53 | Cite as

Open Sesame: treasure in store-operated calcium entry pathway for cancer therapy

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Review Special Topic: Calcium signaling
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Abstract

Store-operated Ca2+ entry (SOCE) controls intracellular Ca2+ homeostasis and regulates a wide range of cellular events including proliferation, migration and invasion. The discovery of STIM proteins as Ca2+ sensors and Orai proteins as Ca2+ channel pore forming units provided molecular tools to understand the physiological function of SOCE. Many studies have revealed the pathophysiological roles of Orai and STIM in tumor cells. This review focuses on recent advances in SOCE and its contribution to tumorigenesis. Altered Orai and/or STIM functions may serve as biomarkers for cancer prognosis, and targeting the SOCE pathway may provide a novel means for cancer treatment.

Keywords

Orai1 STIM1 Ca2+ oscillations proliferation metastasis oncogenic 
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References

  1. 1.
    Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol, 2003, 4: 517–529PubMedCrossRefGoogle Scholar
  2. 2.
    Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol, 2000, 1: 11–21PubMedCrossRefGoogle Scholar
  3. 3.
    Hajnoczky G, Davies E, Madesh M. Calcium signaling and apoptosis. Biochem Biophys Res Commun, 2003, 304: 445–454PubMedCrossRefGoogle Scholar
  4. 4.
    Lipskaia L, Lompre AM. Alteration in temporal kinetics of Ca2+ signaling and control of growth and proliferation. Biol Cell, 2004, 96: 55–68PubMedCrossRefGoogle Scholar
  5. 5.
    Rizzuto R, Pinton P, Ferrari D, Chami M, Szabadkai G, Magalhaes PJ, Di Virgilio F, Pozzan T. Calcium and apoptosis: facts and hypotheses. Oncogene, 2003, 22: 8619–8627PubMedCrossRefGoogle Scholar
  6. 6.
    Bell N, Hann V, Redfern CP, Cheek TR. Store-operated Ca(2+) entry in proliferating and retinoic acid-differentiated N- and S-type neuroblastoma cells. Biochim Biophys Acta, 2013, 1833: 643–651PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Bergmeier W, Weidinger C, Zee I, Feske S. Emerging roles of store-operated Ca(2+) entry through stim and orai proteins in immunity, hemostasis and cancer. Channels (Austin), 2013, 7: 379–391CrossRefGoogle Scholar
  8. 8.
    Barr VA, Bernot KM, Srikanth S, Gwack Y, Balagopalan L, Regan CK, Helman DJ, Sommers CL, Oh-Hora M, Rao A, Samelson LE. Dynamic movement of the calcium sensor STIM1 and the calcium channel Orai1 in activated T-cells: puncta and distal caps. Mol Biol Cell, 2008, 19: 2802–2817PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Chen YF, Chiu WT, Chen YT, Lin PY, Huang HJ, Chou CY, Chang HC, Tang MJ, Shen MR. Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis. Proc Natl Acad Sci USA, 2011, 108: 15225–15230PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Chen YT, Chen YF, Chiu WT, Liu KY, Liu YL, Chang JY, Chang HC, Shen MR. Microtubule-associated histone deacetylase 6 supports the calcium store sensor STIM1 in mediating malignant cell behaviors. Cancer Res, 2013, 73: 4500–4509PubMedCrossRefGoogle Scholar
  11. 11.
    Feng M, Grice DM, Faddy HM, Nguyen N, Leitch S, Wang Y, Muend S, Kenny PA, Sukumar S, Roberts-Thomson SJ, Monteith GR, Rao R. Store-independent activation of Orai1 by SPCA2 in mammary tumors. Cell, 2010, 143: 84–98PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Motiani RK, Hyzinski-Garcia MC, Zhang X, Henkel MM, Abdullaev IF, Kuo YH, Matrougui K, Mongin AA, Trebak M. STIM1 and Orai1 mediate CRAC channel activity and are essential for human glioblastoma invasion. Pflugers Arch, 2013, 465: 1249–1260PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Srikanth S, Gwack Y. Orai1-NFAT signalling pathway triggered by T cell receptor stimulation. Mol Cells, 2013, 35: 182–194PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Yang N, Tang Y, Wang F, Zhang H, Xu D, Shen Y, Sun S, Yang G. Blockade of store-operated Ca(2+) entry inhibits hepatocarcinoma cell migration and invasion by regulating focal adhesion turnover. Cancer Lett, 2013, 330: 163–169PubMedCrossRefGoogle Scholar
  15. 15.
    Yang S, Zhang JJ, Huang XY. Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell, 2009, 15: 124–134PubMedCrossRefGoogle Scholar
  16. 16.
    Lewis RS. Calcium oscillations in T-cells: mechanisms and consequences for gene expression. Biochem Soc Trans, 2003, 31: 925–929PubMedCrossRefGoogle Scholar
  17. 17.
    Giannone G, Ronde P, Gaire M, Haiech J, Takeda K. Calcium oscillations trigger focal adhesion disassembly in human U87 astrocytoma cells. J Biol Chem, 2002, 277: 26364–26371PubMedCrossRefGoogle Scholar
  18. 18.
    Ronde P, Giannone G, Gerasymova I, Stoeckel H, Takeda K, Haiech J. Mechanism of calcium oscillations in migrating human astrocytoma cells. Biochim Biophys Acta, 2000, 1498: 273–280PubMedCrossRefGoogle Scholar
  19. 19.
    Parekh AB, Putney JW Jr. Store-operated calcium channels. Physiol Rev, 2005, 85: 757–810PubMedCrossRefGoogle Scholar
  20. 20.
    Putney JW Jr. A model for receptor-regulated calcium entry. Cell Calcium, 1986, 7: 1–12PubMedCrossRefGoogle Scholar
  21. 21.
    Mercer JC, Dehaven WI, Smyth JT, Wedel B, Boyles RR, Bird GS, Putney JW Jr. Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, STIM1. J Biol Chem, 2006, 281: 24979–24990PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Moreau B, Straube S, Fisher RJ, Putney JW Jr., Parekh AB. Ca2+-calmodulin-dependent facilitation and Ca2+ inactivation of Ca2+ release-activated Ca2+ channels. J Biol Chem, 2005, 280: 8776–8783PubMedCrossRefGoogle Scholar
  23. 23.
    Putney JWJ, Broad LM, Braun FJ, Lievremont JP, Bird GS. Mechanisms of capacitative calcium entry. J Cell Sci, 2001, 114: 2223–2229PubMedGoogle Scholar
  24. 24.
    Wedel B, Boyles RR, Putney JW, Bird GS. Role of the store-operated calcium entry proteins, STIM1 and Orai1, in muscarinic-cholinergic receptor stimulated calcium oscillations in human embryonic kidney cells. J Physiol, 2007, 579: 679–689PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Hoth M, Penner R. Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature, 1992, 355: 353–356PubMedCrossRefGoogle Scholar
  26. 26.
    Zhang SL, Yu Y, Roos J, Kozak JA, Deerinck TJ, Ellisman MH, Stauderman KA, Cahalan MD. STIM1 is a Ca2+ sensor that activates crac channels and migrates from the Ca2+ store to the plasma membrane. Nature, 2005, 437: 902–905PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr., Meyer T. STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol, 2005, 15: 1235–1241PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Velicelebi G, Stauderman KA. STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol, 2005, 169: 435–445PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Yeromin AV, Zhang SL, Jiang W, Yu Y, Safrina O, Cahalan MD. Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature, 2006, 443: 226–229PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Prakriya M, Feske S, Gwack Y, Srikanth S, Rao A, Hogan PG. Orai1 is an essential pore subunit of the CRAC channel. Nature, 2006, 443: 230–233PubMedCrossRefGoogle Scholar
  31. 31.
    Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science, 2006, 312: 1220–1223PubMedCrossRefGoogle Scholar
  32. 32.
    Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature, 2006, 441: 179–185PubMedCrossRefGoogle Scholar
  33. 33.
    Luik RM, Wu MM, Buchanan J, Lewis RS. The elementary unit of store-operated Ca2+ entry: local activation of CRAC channels by STIM1 at ER-plasma membrane junctions. J Cell Biol, 2006, 174: 815–825PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Wu MM, Buchanan J, Luik RM, Lewis RS. Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane. J Cell Biol, 2006, 174: 803–813PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Ong HL, Cheng KT, Liu X, Bandyopadhyay BC, Paria BC, Soboloff J, Pani B, Gwack Y, Srikanth S, Singh BB, Gill D, Ambudkar IS. Dynamic assembly of TRPC1/STIM1/Orai1 ternary complex is involved in store operated calcium influx: evidence for similarities in SOC and CRAC channel components. J Biol Chem, 2007, 282: 9105–9116PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Vig M, Beck A, Billingsley JM, Lis A, Parvez S, Peinelt C, Koomoa DL, Soboloff J, Gill DL, Fleig A, Kinet JP, Penner R. CRACM1 multimers form the ion-selective pore of the CRAC channel. Curr Biol, 2006, 16: 2073–2079PubMedCrossRefGoogle Scholar
  37. 37.
    Soboloff J, Spassova MA, Hewavitharana T, He LP, Xu W, Johnstone LS, Dziadek MA, Gill DL. STIM2 is an inhibitor of STIM1-mediated store-operated Ca2+ entry. Curr Biol, 2006, 16: 1465–1470PubMedCrossRefGoogle Scholar
  38. 38.
    Soboloff J, Spassova MA, Tang XD, Hewavitharana T, Xu W, Gill DL. Orai1 and STIM reconstitute store-operated calcium channel function. J Biol Chem, 2006, 281: 20661–20665PubMedCrossRefGoogle Scholar
  39. 39.
    Spassova MA, Soboloff J, He LP, Xu W, Dziadek MA, Gill DL. STIM1 has a plasma membrane role in the activation of store-operated Ca(2+) channels. Proc Natl Acad Sci USA, 2006, 103: 4040–4045PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Huang GN, Zeng W, Kim JY, Yuan JP, Han L, Muallem S, Worley PF. STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels. Nat Cell Biol, 2006, 8: 1003–1010PubMedCrossRefGoogle Scholar
  41. 41.
    Ma J, Pan Z. Retrograde activation of store-operated calcium channel. Cell Calcium, 2003, 33: 375–384PubMedCrossRefGoogle Scholar
  42. 42.
    Patton AM, Kassis J, Doong H, Kohn EC. Calcium as a molecular target in angiogenesis. Curr Pharm Des, 2003, 9: 543–551PubMedCrossRefGoogle Scholar
  43. 43.
    Guo L, Li ZS, Wang HL, Ye CY, Zhang DC. Carboxyamido-triazole inhibits proliferation of human breast cancer cells via G(2)/M cell cycle arrest and apoptosis. Eur J Pharmacol, 2006, 538: 15–22PubMedCrossRefGoogle Scholar
  44. 44.
    Perabo FG, Demant AW, Wirger A, Schmidt DH, Sitia M, Wardelmann E, Muller SC, Kohn EC. Carboxyamido-triazole (CAI) reverses the balance between proliferation and apoptosis in a rat bladder cancer model. Anticancer Res, 2005, 25: 725–729PubMedGoogle Scholar
  45. 45.
    Ge S, Rempel SA, Divine G, Mikkelsen T. Carboxyamido-triazole induces apoptosis in bovine aortic endothelial and human glioma cells. Clin Cancer Res, 2000, 6: 1248–1254PubMedGoogle Scholar
  46. 46.
    Mignen O, Brink C, Enfissi A, Nadkarni A, Shuttleworth TJ, Giovannucci DR, Capiod T. Carboxyamidotriazole-induced inhibition of mitochondrial calcium import blocks capacitative calcium entry and cell proliferation in HEK-293 cells. J Cell Sci, 2005, 118: 5615–5623PubMedCrossRefGoogle Scholar
  47. 47.
    Enfissi A, Prigent S, Colosetti P, Capiod T. The blocking of capacitative calcium entry by 2-aminoethyl diphenylborate (2-APB) and carboxyamidotriazole (CAI) inhibits proliferation in Hep G2 and Huh-7 human hepatoma cells. Cell calcium, 2004, 36: 459–467PubMedCrossRefGoogle Scholar
  48. 48.
    Padar S, Bose DD, Livesey JC, Thomas DW. 2-aminoethoxydiphenyl borate perturbs hormone-sensitive calcium stores and blocks store-operated calcium influx pathways independent of cytoskeletal disruption in human A549 lung cancer cells. Biochem Pharmacol, 2005, 69: 1177–1186PubMedCrossRefGoogle Scholar
  49. 49.
    Kazerounian S, Pitari GM, Shah FJ, Frick GS, Madesh M, Ruiz-Stewart I, Schulz S, Hajnoczky G, Waldman SA. Proliferative signaling by store-operated calcium channels opposes colon cancer cell cytostasis induced by bacterial enterotoxins. J Pharmacol Exp Ther, 2005, 314: 1013–1022PubMedCrossRefGoogle Scholar
  50. 50.
    Koslowski M, Sahin U, Dhaene K, Huber C, Tureci O. MS4A12 is a colon-selective store-operated calcium channel promoting malignant cell processes. Cancer Res, 2008, 68: 3458–3466PubMedCrossRefGoogle Scholar
  51. 51.
    Vanden Abeele F, Roudbaraki M, Shuba Y, Skryma R, Prevarskaya N. Store-operated Ca2+ current in prostate cancer epithelial cells. Role of endogenous Ca2+ transporter type 1. J Biol Chem, 2003, 278: 15381–15389CrossRefGoogle Scholar
  52. 52.
    Vanden Abeele F, Shuba Y, Roudbaraki M, Lemonnier L, Vanoverberghe K, Mariot P, Skryma R, Prevarskaya N. Store-operated Ca2+ channels in prostate cancer epithelial cells: function, regulation, and role in carcinogenesis. Cell Calcium, 2003, 33: 357–373CrossRefGoogle Scholar
  53. 53.
    Skryma R, Mariot P, Bourhis XL, Coppenolle FV, Shuba Y, Vanden Abeele F, Legrand G, Humez S, Boilly B, Prevarskaya N. Store depletion and store-operated Ca2+ current in human prostate cancer lncap cells: involvement in apoptosis. J Physiol, 2000, 527 (Pt 1): 71–83CrossRefGoogle Scholar
  54. 54.
    Pigozzi D, Ducret T, Tajeddine N, Gala JL, Tombal B, Gailly P. Calcium store contents control the expression of TRPC1, TRPC3 and TRPV6 proteins in lncap prostate cancer cell line. Cell Calcium, 2006, 39: 401–415PubMedCrossRefGoogle Scholar
  55. 55.
    Pan Z, Bhat MB, Nieminen AL, Ma J. Synergistic movements of Ca(2+) and Bax in cells undergoing apoptosis. J Biol Chem, 2001, 276: 32257–32263PubMedCrossRefGoogle Scholar
  56. 56.
    Lin PH, Pan Z, Zheng L, Li N, Danielpour D, Ma JJ. Overexpression of Bax sensitizes prostate cancer cells to TGF-beta induced apoptosis. Cell Res, 2005, 15: 160–166PubMedCrossRefGoogle Scholar
  57. 57.
    Kokoska ER, Smith GS, Miller TA. Nonsteroidal anti-inflammatory drugs attenuate proliferation of colonic carcinoma cells by blocking epidermal growth factor-induced Ca++ mobilization. J Gastrointest Surg, 2000, 4: 150–161PubMedCrossRefGoogle Scholar
  58. 58.
    Berna-Erro A, Woodard GE, Rosado JA. Orais and STIMs: physiological mechanisms and disease. J Cell Mol Med, 2012, 16: 407–424PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Feske S. Immunodeficiency due to defects in store-operated calcium entry. Ann New York Acad Sci, 2011, 1238: 74–90CrossRefGoogle Scholar
  60. 60.
    Fuchs S, Rensing-Ehl A, Speckmann C, Bengsch B, Schmitt-Graeff A, Bondzio I, Maul-Pavicic A, Bass T, Vraetz T, Strahm B, Ankermann T, Benson M, Caliebe A, Folster-Holst R, Kaiser P, Thimme R, Schamel WW, Schwarz K, Feske S, Ehl S. Antiviral and regulatory T cell immunity in a patient with stromal interaction molecule 1 deficiency. J Immunol, 2012, 188: 1523–1533PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Le Deist F, Capiod T. Immunodeficiencies and pathologies associated with mutations in STIM/Orai, a membrane complex in the heart of calcium signalling. Med Sci, 2011, 27: 737–745Google Scholar
  62. 62.
    Shaw PJ, Feske S. Physiological and pathophysiological functions of SOCE in the immune system. Front Biosci (Elite Ed), 2012, 4: 2253–2268CrossRefGoogle Scholar
  63. 63.
    Verbsky JW, Chatila TA. T-regulatory cells in primary immune deficiencies. Curr Opin Allergy Clin Immunol, 2011, 11: 539–544PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Motiani RK, Hyzinski-Garcia MC, Zhang X, Henkel MM, Abdullaev IF, Kuo YH, Matrougui K, Mongin AA, Trebak M. STIM1 and Orai1 mediate CRAC channel activity and are essential for human glioblastoma invasion. Pflugers Arch, 2013, 465: 1249–1260PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Kondratska K, Kondratskyi A, Yassine M, Lemonnier L, Lepage G, Morabito A, Skryma R, Prevarskaya N. Orai1 and STIM1 mediate SOCE and contribute to apoptotic resistance of pancreatic adenocarcinoma. Biochim Biophys Acta, 2014, 1843: 2263–2269PubMedCrossRefGoogle Scholar
  66. 66.
    Flourakis M, Lehen’kyi V, Beck B, Raphael M, Vandenberghe M, Abeele FV, Roudbaraki M, Lepage G, Mauroy B, Romanin C, Shuba Y, Skryma R, Prevarskaya N. Orai1 contributes to the establishment of an apoptosis-resistant phenotype in prostate cancer cells. Cell Death Dis, 2010, 1: e75PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Dubois C, Vanden Abeele F, Lehen’kyi V, Gkika D, Guarmit B, Lepage G, Slomianny C, Borowiec AS, Bidaux G, Benahmed M, Shuba Y, Prevarskaya N. Remodeling of channel-forming Orai proteins determines an oncogenic switch in prostate cancer. Cancer cell, 2014, 26: 19–32PubMedCrossRefGoogle Scholar
  68. 68.
    Zhu H, Zhang H, Jin F, Fang M, Huang M, Yang CS, Chen T, Fu L, Pan Z. Elevated Orai1 expression mediates tumor-promoting intracellular Ca2+ oscillations in human esophageal squamous cell carcinoma. Oncotarget, 2014, 5: 3455–3471PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Kim JH, Lkhagvadorj S, Lee MR, Hwang KH, Chung HC, Jung JH, Cha SK, Eom M. Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma. Biochem Biophys Res Commun, 2014, 448: 76–82PubMedCrossRefGoogle Scholar
  70. 70.
    Weidinger C, Shaw PJ, Feske S. STIM1 and STIM2-mediated Ca(2+) influx regulates antitumour immunity by CD8(+) T cells. EMBO Mol Med, 2013, 5: 1311–1321PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Oh-Hora M, Yamashita M, Hogan PG, Sharma S, Lamperti E, Chung W, Prakriya M, Feske S, Rao A. Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nat Immunol, 2008, 9: 432–443PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Motiani RK, Zhang X, Harmon KE, Keller RS, Matrougui K, Bennett JA, Trebak M. Orai3 is an estrogen receptor α-regulated Ca2+ channel that promotes tumorigenesis. FASEB J, 2013, 27: 63–75PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Ay AS, Benzerdjerb N, Sevestre H, Ahidouch A, Ouadid-Ahidouch H. Orai3 constitutes a native store-operated calcium entry that regulates non small cell lung adenocarcinoma cell proliferation. PLoS One, 2013, 8: e72889PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Chantome A, Potier-Cartereau M, Clarysse L, Fromont G, Marionneau-Lambot S, Gueguinou M, Pages JC, Collin C, Oullier T, Girault A, Arbion F, Haelters JP, Jaffres PA, Pinault M, Besson P, Joulin V, Bougnoux P, Vandier C. Pivotal role of the lipid Raft SK3-Orai1 complex in human cancer cell migration and bone metastases. Cancer Res, 2013, 73: 4852–4861PubMedCrossRefGoogle Scholar
  75. 75.
    Hou X, Pedi L, Diver MM, Long SB. Crystal structure of the calcium release-activated calcium channel Orai. Science, 2012, 338: 1308–1313PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Li Z, Liu L, Deng Y, Ji W, Du W, Xu P, Chen L, Xu T. Graded activation of CRAC channel by binding of different numbers of STIM1 to Orai1 subunits. Cell Res, 2011, 21: 305–315PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Hoover PJ, Lewis RS. Stoichiometric requirements for trapping and gating of Ca2+ release-activated Ca2+ (CRAC) channels by stromal interaction molecule 1 (STIM1). Proc Natl Acad Sci USA, 2011, 108: 13299–13304PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Wang X, Wang Y, Zhou Y, Hendron E, Mancarella S, Andrake MD, Rothberg BS, Soboloff J, Gill DL. Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site. Nat Commun, 2014, 5: 3183PubMedPubMedCentralGoogle Scholar

Copyright information

© The Author(s) 2014

Authors and Affiliations

  1. 1.Department of Internal MedicineThe Ohio State University Wexner Medical CenterColumbusUSA
  2. 2.Department of SurgeryThe Ohio State University Wexner Medical CenterColumbusUSA
  3. 3.Comprehensive Cancer CenterThe Ohio State University Wexner Medical CenterColumbusUSA
  4. 4.Davis Heart and Lung Research InstituteThe Ohio State University Wexner Medical CenterColumbusUSA

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