Neurochemical Research

, Volume 36, Issue 7, pp 1157–1165 | Cite as

The Physiological Function of Store-operated Calcium Entry

  • James W. Putney
Original Paper


Store-operated Ca2+ entry is a process whereby the depletion of intracellular Ca2+ stores signals the opening of plasma membrane Ca2+ channels. It has long been thought that the main function of store-operated Ca2+ entry was the replenishment of intracellular Ca2+ stores following their discharge during intracellular Ca2+ signaling. Recent results, however, suggest that the primary function of these channels may be to provide direct Ca2+ signals to recipients localized to spatially restricted areas close to the sites of Ca2+ entry in order to initiate specific signaling pathways.


Calcium channels Store-operated channels Calcium signaling Ion channels Orai STIM Calcium oscillations 



Drs. Stephen Shears and David Armstrong read the manuscript and provided helpful comments. Work from the author’s laboratory discussed in this review was supported by the Intramural Program of the National Institutes of Health, NIEHS.


  1. 1.
    Bohr DF (1973) Vascular smooth muscle updated. Circ Res 32:665–672PubMedGoogle Scholar
  2. 2.
    Putney JW, Poggioli J, Weiss SJ (1981) Receptor regulation of calcium release and calcium permeability in parotid gland cells. Philos Trans R Soc Lond B 296:37–45Google Scholar
  3. 3.
    Putney JW (1977) Muscarinic, alpha-adrenergic and peptide receptors regulate the same calcium influx sites in the parotid gland. J Physiol (Lond) 268:139–149Google Scholar
  4. 4.
    Parod RJ, Putney JW (1978) The role of calcium in the receptor mediated control of potassium permeability in the rat lacrimal gland. J Physiol (Lond) 281:371–381Google Scholar
  5. 5.
    Casteels R, Droogmans G (1981) Exchange characteristics of the noradrenaline-sensitive calcium store in vascular smooth muscle cells of rabbit ear artery. J Physiol (Lond) 317:263–279Google Scholar
  6. 6.
    Berridge MJ (1983) Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol. Biochem J 212:849–858PubMedGoogle Scholar
  7. 7.
    Streb H, Irvine RF, Berridge MJ et al (1983) Release of Ca2+ from a nonmitochondrial store in pancreatic cells by inositol-1,4,5-trisphosphate. Nature 306:67–68PubMedGoogle Scholar
  8. 8.
    Slack BE, Bell JE, Benos DJ (1986) Inositol 1,4,5-trisphosphate injection mimics fertilization potentials in sea urchin eggs. Am J Physiol 250:C340–C344PubMedGoogle Scholar
  9. 9.
    Bird GStJ, Rossier MF, Hughes AR et al (1991) Activation of Ca2+ entry into acinar cells by a non-phosphorylatable inositol trisphosphate. Nature 352:162–165PubMedGoogle Scholar
  10. 10.
    Ueda T, Church SH, Noel MW et al (1986) Influence of inositol 1,4,5-trisphosphate and guanine nucleotides on intracellular calcium release within the N1E–115 neuronal cell line. J Biol Chem 261:3184–3192PubMedGoogle Scholar
  11. 11.
    Putney JW (1986) A model for receptor-regulated calcium entry. Cell Calcium 7:1–12PubMedGoogle Scholar
  12. 12.
    Takemura H, Putney JW (1989) Capacitative calcium entry in parotid acinar cells. Biochem J 258:409–412PubMedGoogle Scholar
  13. 13.
    Rasmussen U, Christensen SB, Sandberg F (1978) Thapsigargin and thapsigargicin, two new histamine liberators from thapsia garganica. Acta Pharmaceut Suec 15:133–140Google Scholar
  14. 14.
    Jackson TR, Patterson SI, Thastrup O et al (1988) A novel tumour promoter, thapsigargin, transiently increases cytoplasmic free Ca2+ without generation of inositol phosphates in NG115–401L neuronal cells. Biochem J 253:81–86PubMedGoogle Scholar
  15. 15.
    Takemura H, Hughes AR, Thastrup O et al (1989) Activation of calcium entry by the tumor promoter, thapsigargin, in parotid acinar cells. Evidence that an intracellular calcium pool, and not an inositol phosphate, regulates calcium fluxes at the plasma membrane. J Biol Chem 264:12266–12271PubMedGoogle Scholar
  16. 16.
    Thastrup O, Cullen PJ, Drobak BK et al (1990) Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. Proc Nat Acad Sci USA 87:2466–2470PubMedGoogle Scholar
  17. 17.
    Putney JW (1990) Capacitative calcium entry revisited. Cell Calcium 11:611–624PubMedGoogle Scholar
  18. 18.
    Hoth M, Penner R (1992) Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature 355:353–355PubMedGoogle Scholar
  19. 19.
    Lewis RS, Cahalan MD (1989) Mitogen-induced oscillations of cytosolic Ca2+ and transmembrane Ca2+ current. Cell Reg 1:99–112Google Scholar
  20. 20.
    Zweifach A, Lewis RS (1993) Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores. Proc Nat Acad Sci USA 90:6295–6299PubMedGoogle Scholar
  21. 21.
    Parekh AB, Putney JW (2005) Store-operated calcium channels. Physiol Rev 85:757–810PubMedGoogle Scholar
  22. 22.
    Cosens DJ, Manning A (1969) Abnormal electroretinogram from a Drosophila mutant. Nature 224:285–287PubMedGoogle Scholar
  23. 23.
    Montell C, Rubin GM (1989) Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2:1313–1323PubMedGoogle Scholar
  24. 24.
    Hardie RC, Minke B (1993) Novel Ca2+ channels underlying transduction in Drosophila photoreceptors: implications for phosphoinositide-mediated Ca2+ mobilization. Trends Neurosci 16:371–376PubMedGoogle Scholar
  25. 25.
    Zhu X, Chu PB, Peyton M et al (1995) Molecular cloning of a widely expressed human homologue for the Drosophila trp gene. FEBS Lett 373:193–198PubMedGoogle Scholar
  26. 26.
    Wes PD, Chevesich J, Jeromin A et al (1995) TRPC1, a human homolog of a Drosophila store-operated channel. Proc Nat Acad Sci USA 92:9652–9656PubMedGoogle Scholar
  27. 27.
    Montell C, Birnbaumer L, Flockerzi V et al (2002) A unified nomenclature for the superfamily of TRP cation channels. Mol Cell 9:229–231PubMedGoogle Scholar
  28. 28.
    Hurst RS, Zhu X, Boulay G et al (1998) Ionic currents underlying HTRP3 mediated agonist-dependent Ca2+ influx in stably transfected HEK293 cells. FEBS Lett 422:333–338PubMedGoogle Scholar
  29. 29.
    Kiselyov K, Xu X, Mozhayeva G et al (1998) Functional interaction between InsP3 receptors and store-operated Htrp3 channels. Nature 396:478–482PubMedGoogle Scholar
  30. 30.
    Liu X, Wang W, Singh BB et al (2000) Trp1, a candidate protein for the store-operated Ca2+ influx mechanism in salivary gland cells. J Biol Chem 275:3403–3411PubMedGoogle Scholar
  31. 31.
    Xu SZ, Beech DJ (2001) TrpC1 is a membrane-spanning subunit of store-operated Ca(2+) channels in native vascular smooth muscle cells. Circ Res 88:84–87PubMedGoogle Scholar
  32. 32.
    Rosado JA, Sage SO (2000) Coupling between inositol 1,4,5-trisphosphate receptors and human transient receptor potential channel 1 when intracellular Ca2+ stores are depleted. Biochem J 350:631–635PubMedGoogle Scholar
  33. 33.
    Vazquez G, Lièvremont J-P, Bird GStJ et al (2001) Human Trp3 forms both inositol trisphosphate receptor-dependent and receptor-independent store-operated cation channels in DT40 avian B-lymphocytes. Proc Nat Acad Sci USA 98:11777–11782PubMedGoogle Scholar
  34. 34.
    Lievremont JP, Bird GS, Putney JW (2004) Canonical transient receptor potential TRPC7 can function as both a receptor- and store-operated channel in HEK-293 cells. Am J Physiol Cell Physiol 287:C1709–C1716PubMedGoogle Scholar
  35. 35.
    Trebak M, Bird GStJ, McKay RR et al (2003) Signaling mechanism for receptor-activated TRPC3 channels. J Biol Chem 278:16244–16252PubMedGoogle Scholar
  36. 36.
    Huang GN, Zeng W, Kim JY et al (2006) STIM1 carboxyl-terminus activates native SOC, Icrac and TRPC1 channels. Nat Cell Biol 8:1003–1010PubMedGoogle Scholar
  37. 37.
    DeHaven WI, Jones BF, Petranka JG et al (2009) TRPC channels function independently of STIM1 and Orai1. J Physiol 587:2275–2298PubMedGoogle Scholar
  38. 38.
    Rosado JA, Brownlow SL, Sage SO (2002) Endogenously expressed Trp1 is involved in store-mediated Ca2+ entry by conformational coupling in human platelets. J Biol Chem 277:42157–42163PubMedGoogle Scholar
  39. 39.
    Hassock SR, Zhu MX, Trost C et al (2002) Expression and role of TRPC proteins in human platelets: evidence that TRPC6 forms the store-independent calcium entry channel. Blood 100:2801–2811PubMedGoogle Scholar
  40. 40.
    Varga-Szabo D, Authi KS, Braun A et al (2008) Store-operated Ca(2+) entry in platelets occurs independently of transient receptor potential (TRP) C1. Pflugers Arch 457:377–387PubMedGoogle Scholar
  41. 41.
    Hofmann T, Schaefer M, Schultz G et al (2000) Transient receptor potential channels as molecular substrates of receptor-mediated cation entry. J Mol Med 78:14–25PubMedGoogle Scholar
  42. 42.
    Vazquez G, Wedel BJ, Aziz O et al (2004) The mammalian TRPC cation channels. Biochim Biophys Acta 1742:21–36PubMedGoogle Scholar
  43. 43.
    Hardie RC (2003) Regulation of trp channels via lipid second messengers. Ann Rev Physiol 65:735–759Google Scholar
  44. 44.
    Hofmann T, Obukhov AG, Schaefer M et al (1999) Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397:259–262PubMedGoogle Scholar
  45. 45.
    Lemonnier L, Trebak M, Putney JW Jr (2008) Complex regulation of the TRPC3, 6 and 7 channel subfamily by diacylglycerol and phosphatidylinositol-4,5-bisphosphate. Cell Calcium 43:506–514PubMedGoogle Scholar
  46. 46.
    Trebak M, Lemonnier L, DeHaven WI et al (2009) Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels. Pflugers Arch 457:757–769PubMedGoogle Scholar
  47. 47.
    Hofmann T, Schaefer M, Schultz G et al (2002) Subunit composition of mammalian transient receptor potential channels in living cells. Proc Nat Acad Sci USA 99:7461–7466PubMedGoogle Scholar
  48. 48.
    Strübing C, Krapivinsky G, Krapivinsky L et al (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29:645–655PubMedGoogle Scholar
  49. 49.
    Cheng KT, Liu X, Ong HL et al (2008) Functional requirement for Orai1 in store-operated TRPC1-STIM1 channels. J Biol Chem 283:12935–12940PubMedGoogle Scholar
  50. 50.
    Zhang SL, Yu Y, Roos J et al (2005) STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437:902–905PubMedGoogle Scholar
  51. 51.
    Liou J, Kim ML, Heo WD et al (2005) STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol 15:1235–1241PubMedGoogle Scholar
  52. 52.
    Dziadek MA, Johnstone LS (2007) Biochemical properties and cellular localisation of STIM proteins. Cell Calcium 42:123–132PubMedGoogle Scholar
  53. 53.
    Mercer JC, DeHaven WI, Smyth JT et al (2006) Large store-operated calcium-selected currents due to co-expression of orai1 or orai2 with the intracellular calcium sensor, stim1. J Biol Chem 281:24979–24990PubMedGoogle Scholar
  54. 54.
    Wu MM, Buchanan J, Luik RM et al (2006) Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane. J Cell Biol 174:803–813PubMedGoogle Scholar
  55. 55.
    Baba Y, Hayashi K, Fujii Y et al (2006) Coupling of STIM1 to store-operated Ca2+ entry through its constitutive and inducible movement in the endoplasmic reticulum. Proc Nat Acad Sci USA 103:16704–16709PubMedGoogle Scholar
  56. 56.
    Liou J, Fivaz M, Inoue T et al (2007) Live-cell imaging reveals sequential oligomerization and local plasma membrane targeting of stromal interaction molecule 1 after Ca2+ store depletion. Proc Natl Acad Sci USA 104:9301–9306PubMedGoogle Scholar
  57. 57.
    Feske S, Gwack Y, Prakriya M et al (2006) A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441:179–185PubMedGoogle Scholar
  58. 58.
    Vig M, Peinelt C, Beck A et al (2006) CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science 312:1220–1223PubMedGoogle Scholar
  59. 59.
    Zhang SL, Yeromin AV, Zhang XH et al (2006) Genome-wide RNAi screen of Ca2+ influx identifies genes that regulate Ca2+ release-activated Ca2+ channel activity. Proc Natl Acad Sci USA 103:9357–9362PubMedGoogle Scholar
  60. 60.
    Parekh AB, Penner R (1997) Store depletion and calcium influx. Physiol Rev 77:901–930PubMedGoogle Scholar
  61. 61.
    Peinelt C, Vig M, Koomoa DL et al (2006) Amplification of CRAC current by STIM1 and CRACM1 (Orai1). Nat Cell Biol 8:771–773PubMedGoogle Scholar
  62. 62.
    Soboloff J, Spassova MA, Tang XD et al (2006) Orai1 and STIM reconstitute store-operated calcium channel function. J Biol Chem 281:20661–20665PubMedGoogle Scholar
  63. 63.
    Prakriya M, Feske S, Gwack Y et al (2006) Orai1 is an essential pore subunit of the CRAC channel. Nature 443:230–233PubMedGoogle Scholar
  64. 64.
    Yeromin AV, Zhang SL, Jiang W et al (2006) Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature 443:226–229PubMedGoogle Scholar
  65. 65.
    Vig M, Beck A, Billingsley JM et al (2006) CRACM1 multimers form the ion-selective pore of the CRAC channel. Curr Biol 16:2073–2079PubMedGoogle Scholar
  66. 66.
    Derler I, Fahrner M, Carugo O et al (2009) Increased hydrophobicity at the N terminus/membrane interface impairs gating of the severe combined immunodeficiency-related ORAI1 mutant. J Biol Chem 284:15903–15915PubMedGoogle Scholar
  67. 67.
    Fahrner M, Muik M, Derler I et al (2009) Mechanistic view on domains mediating STIM1-Orai coupling. Immunol Rev 231:99–112PubMedGoogle Scholar
  68. 68.
    Muik M, Frischauf I, Derler I et al (2008) Dynamic coupling of the putative coiled-coil domain of ORAI1 with STIM1 mediates ORAI1 channel activation. J Biol Chem 283:8014–8022PubMedGoogle Scholar
  69. 69.
    Yuan JP, Zeng W, Dorwart MR et al (2009) SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat Cell Biol 11(3):337–343PubMedGoogle Scholar
  70. 70.
    Park CY, Hoover PJ, Mullins FM et al (2009) STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell 136:876–890PubMedGoogle Scholar
  71. 71.
    Muik M, Fahrner M, Derler I et al (2009) A cytosolic homomerization and a modulatory domain within STIM1 C-terminus determine coupling to ORAI1 channels. J Biol Chem 284:8421–8426PubMedGoogle Scholar
  72. 72.
    Kawasaki T, Lange I, Feske S (2009) A minimal regulatory domain in the C terminus of STIM1 binds to and activates ORAI1 CRAC channels. Biochem Biophys Res Commun 385(1):49–54PubMedGoogle Scholar
  73. 73.
    Mullins FM, Park CY, Dolmetsch RE et al (2009) STIM1 and calmodulin interact with Orai1 to induce Ca2+-dependent inactivation of CRAC channels. Proc Natl Acad Sci 106:15495–15500PubMedGoogle Scholar
  74. 74.
    Smyth JT, Petranka JG, Boyles RR et al (2009) Phosphorylation of STIM1 underlies suppression of store-operated calcium entry during mitosis. Nat Cell Biol 11:1465–1472PubMedGoogle Scholar
  75. 75.
    Yang S, Zhang JJ, Huang XY (2009) Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell 15:124–134PubMedGoogle Scholar
  76. 76.
    Abdullaev IF, Bisaillon JM, Potier M et al (2008) Stim1 and Orai1 mediate CRAC currents and store-operated calcium entry important for endothelial cell proliferation. Circ Res 103:1289–1299PubMedGoogle Scholar
  77. 77.
    Stiber J, Hawkins A, Zhang ZS et al (2008) STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle. Nat Cell Biol 10:688–697PubMedGoogle Scholar
  78. 78.
    Berra-Romani R, Mazzocco-Spezzia A, Pulina MV et al (2008) Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture. Am J Physiol Cell Physiol 295(3):C779–C790PubMedGoogle Scholar
  79. 79.
    Potier M, Gonzalez JC, Motiani RK et al (2009) Evidence for STIM1- and Orai1-dependent store-operated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration. FASEB J 23:2425–2437PubMedGoogle Scholar
  80. 80.
    Partiseti M, Le Deist F, Hivroz C et al (1994) The calcium current activated by T cell receptor and store depletion in human lymphocytes is absent in a primary immunodeficiency. J Biol Chem 269:32327–32335PubMedGoogle Scholar
  81. 81.
    Feske S, Prakriya M, Rao A et al (2005) A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients. J Exp Med 202:651–662PubMedGoogle Scholar
  82. 82.
    Feske S (2010) CRAC channelopathies. Pflugers Arch 460(2):417–435PubMedGoogle Scholar
  83. 83.
    Feske S, Picard C, Fischer A (2010) Immunodeficiency due to mutations in ORAI1 and STIM1. Clin Immunol 135:169–182PubMedGoogle Scholar
  84. 84.
    Merritt JE, Rink TJ (1987) Regulation of cytosolic free calcium in fura-2-loaded rat parotid acinar cells. J Biol Chem 262:17362–17369PubMedGoogle Scholar
  85. 85.
    Berridge MJ (1990) Calcium oscillations. J Biol Chem 265:9583–9586PubMedGoogle Scholar
  86. 86.
    Dupont G, Combettes L, Leybaert L (2007) Calcium dynamics: spatio-temporal organization from the subcellular to the organ level. Int Rev Cytol 261:193–245PubMedGoogle Scholar
  87. 87.
    Thomas AP, Bird GStJ, Hajnóczky G et al (1996) Spatial and temporal aspects of cellular calcium signalling. FASEB J 10:1505–1517PubMedGoogle Scholar
  88. 88.
    Bird GS, Putney JW (2005) Capacitative calcium entry supports calcium oscillations in human embryonic kidney cells. J Physiol 562:697–706PubMedGoogle Scholar
  89. 89.
    Shuttleworth TJ (1999) What drives calcium entry during [Ca2+]i oscillations?–challenging the capacitative model. Cell Calcium 25:237–246PubMedGoogle Scholar
  90. 90.
    Bird GS, Hwang SY, Smyth JT et al (2009) STIM1 is a calcium sensor specialized for digital signaling. Curr Biol 19:1724–1729PubMedGoogle Scholar
  91. 91.
    Wedel B, Boyles RR, Putney JW et al (2007) 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 579:679–689PubMedGoogle Scholar
  92. 92.
    Gwack Y, Feske S, Srikanth S et al (2007) Signalling to transcription: store-operated Ca2+ entry and NFAT activation in lymphocytes. Cell Calcium 42:145–156PubMedGoogle Scholar
  93. 93.
    Lewis RS (2003) Calcium oscillations in T-cells: mechanisms and consequences for gene expression. Biochem Soc Trans 31:925–929PubMedGoogle Scholar
  94. 94.
    Dolmetsch RE, Lewis RS (1994) Signaling between intracellular Ca2+ stores and depletion-activated Ca2+ channels generates [Ca2+]i oscillations in T lymphocytes. J Gen Physiol 103:365–388PubMedGoogle Scholar
  95. 95.
    Le Deist F, Hivroz C, Partiseti M et al (1995) A primary T-cell immunodeficiency associated with defective transmembrane calcium influx. Blood 85:1053–1062PubMedGoogle Scholar
  96. 96.
    Ng SW, Di Capite J, Singaravelu K et al (2008) Sustained activation of the tyrosine kinase Syk by antigen in mast cells requires local Ca2+ influx through Ca2+ release-activated Ca2+ channels. J Biol Chem 283:31348–31355PubMedGoogle Scholar
  97. 97.
    Ng SW, Nelson C, Parekh AB (2009) Coupling of Ca2+ microdomains to spatially and temporally distinct cellular responses by the tyrosine kinase Syk. J Biol Chem 284:24767–24772PubMedGoogle Scholar
  98. 98.
    Cooper DMF, Yoshimura M, Zhang Y et al (1994) Capacitative Ca2+ entry regulates Ca2+-sensitive adenylyl cyclases. Biochem J 297:437–440PubMedGoogle Scholar
  99. 99.
    Chang WC, Nelson C, Parekh AB (2006) Ca2+ influx through CRAC channels activates cytosolic phospholipase A2, leukotriene C4 secretion, and expression of c-fos through ERK-dependent and -independent pathways in mast cells. FASEB J 20:2381–2383PubMedGoogle Scholar
  100. 100.
    Parekh AB (2008) Ca2+ microdomains near plasma membrane Ca2+ channels: impact on cell function. J Physiol 586:3043–3054PubMedGoogle Scholar
  101. 101.
    Kwan CY, Takemura H, Obie JF et al (1990) Effects of methacholine, thapsigargin and La3+ on plasmalemmal and intracellular Ca2+ transport in lacrimal acinar cells. Am J Physiol 258:C1006–C1015PubMedGoogle Scholar
  102. 102.
    Sneyd J, Tsaneva-Atanasova K, Yule DI et al (2004) Control of calcium oscillations by membrane fluxes. Proc Natl Acad Sci USA 101:1392–1396PubMedGoogle Scholar
  103. 103.
    Van Breemen C, Farinas B, Gerba P et al (1972) Excitation-contraction coupling in rabbit aorta studied by the lanthanum method for measuring cellular calcium influx. Circ Res 30:44–54PubMedGoogle Scholar
  104. 104.
    Di Capite J, Ng SW, Parekh AB (2009) Decoding of cytoplasmic Ca(2+) oscillations through the spatial signature drives gene expression. Curr Biol 19:853–858PubMedGoogle Scholar
  105. 105.
    Berridge MJ, Cobbold PH, Cuthbertson KS (1988) Spatial and temporal aspects of cell signalling. Philos Trans R Soc Lond [Biol] 320:325–343Google Scholar
  106. 106.
    Bootman MD, Lipp P, Berridge MJ (2001) The organisation and functions of local Ca2+ signals. J Cell Sci 114:2213–2222PubMedGoogle Scholar
  107. 107.
    Falcke M (2004) Reading the patterns in living cells–the physics of Ca2+ signaling. Adv Physics 53:255–440Google Scholar
  108. 108.
    Oh-Hora M, Yamashita M, Hogan PG et al (2008) Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nat Immunol 9:432–443PubMedGoogle Scholar
  109. 109.
    Zheng L, Stathopulos PB, Li GY et al (2008) Biophysical characterization of the EF-hand and SAM domain containing Ca2+ sensory region of STIM1 and STIM2. Biochem Biophys Res Commun 369:240–246PubMedGoogle Scholar
  110. 110.
    Parvez S, Beck A, Peinelt C et al (2008) STIM2 protein mediates distinct store-dependent and store-independent modes of CRAC channel activation. FASEB J 22:752–761PubMedGoogle Scholar
  111. 111.
    Brandman O, Liou J, Park WS et al (2007) STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca(2+) levels. Cell 131:1327–1339PubMedGoogle Scholar
  112. 112.
    Soboloff J, Spassova MA, Hewavitharana T et al (2006) STIM2 is an inhibitor of STIM1-mediated store-operated Ca2+ Entry. Curr Biol 16:1465–1470PubMedGoogle Scholar
  113. 113.
    Rizzuto R, Pozzan T (2006) Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiol Rev 86:369–408PubMedGoogle Scholar
  114. 114.
    Nicholls DG (2005) Mitochondria and calcium signaling. Cell Calcium 38:311–317PubMedGoogle Scholar

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© Springer Science+Business Media, LLC (outside the USA)  2011

Authors and Affiliations

  1. 1.National Institute of Environmental Health Sciences—NIH, Department of Health and Human ServicesResearch Triangle ParkUSA

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