Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The cellular and molecular basis of store-operated calcium entry

Nature Cell Biology volume 4, pages E263–E272 (2002)Cite this article

Abstract

The impact of calcium signalling on so many areas of cell biology reflects the crucial role of calcium signals in the control of diverse cellular functions. Despite the precision with which spatial and temporal details of calcium signals have been resolved, a fundamental aspect of the generation of calcium signals — the activation of 'store-operated channels' (SOCs) — remains a molecular and mechanistic mystery. Here we review new insights into the exchange of signals between the endoplasmic reticulum (ER) and plasma membrane that result in activation of calcium entry channels mediating crucial long-term calcium signals.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Coupling models for activation of store-operated channels (SOCs).
Figure 2: Phylogenetic relationship between TRP channels implicated in CCE.
Figure 3: The hypothetical calcium signal-coupling domain.
Figure 4: Coupling of TRP channels expressed in vertebrate cells.

Similar content being viewed by others

References

  1. Berridge, M. J., Bootman, M. D. & Lipp, P. Calcium — a life and death signal. Nature 395, 645–648 (1998).

    CAS  PubMed  Google Scholar 

  2. Berridge, M. J., Lipp, P. & Bootman, M. D. The versatility and universality of calcium signalling. Nature Rev. Mol. Cell Biol. 1, 11–21 (2000).

    Article  CAS  Google Scholar 

  3. Putney, J. W. & McKay, R. R. Capacitative calcium entry channels. Bioessays 21, 38–46 (1999).

    PubMed  Google Scholar 

  4. Clapham, D. E. Calcium signaling. Cell 80, 259–268 (1995).

    CAS  PubMed  Google Scholar 

  5. Berridge, M. J. Capacitative calcium entry. Biochem. J. 312, 1–11 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Putney, J. W. Capacitative calcium entry (Springer, New York, 1997).

    Google Scholar 

  7. Berridge, M. J. Elementary and global aspects of calcium signalling. J.Physiol.(Lond.) 499, 291–306 (1997).

    CAS  Google Scholar 

  8. Parekh, A. B. & Penner, R. Store depletion and calcium influx. Physiol. Rev. 77, 901–930 (1997).

    CAS  PubMed  Google Scholar 

  9. Barritt, G. J. Receptor-activated Ca2+ inflow in animal cells: a variety of pathways tailored to meet different intracellular Ca2+ signalling requirements. Biochem. J. 337, 153–169 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Putney, J. W. & Ribeiro, C. M. Signaling pathways between the plasma membrane and endoplasmic reticulum calcium stores. Cell Mol. Life Sci. 57, 1272–1286 (2000).

    CAS  PubMed  Google Scholar 

  11. Lewis, R. S. Calcium signaling mechanisms in t lymphocytes. Annu. Rev. Immunol. 19, 497–521 (2001).

    CAS  PubMed  Google Scholar 

  12. Putney, J. W. Jr., Broad, L. M., Braun, F. J., Lievremont, J. P., & Bird, G. S. Mechanisms of capacitative calcium entry. J. Cell Sci. 114, 2223–2229 (2001).

    CAS  PubMed  Google Scholar 

  13. Putney, J. W. A model for receptor-regulated calcium entry. Cell Calcium 7, 1–12 (1986).

    CAS  PubMed  Google Scholar 

  14. Putney, J. W. Capacitative calcium entry revisited. Cell Calcium 11, 611–624 (1990).

    CAS  PubMed  Google Scholar 

  15. Gill, D. L. et al. Calcium pools, calcium entry, and cell growth. Biosci. Rep. 16, 139–157 1996).

    CAS  PubMed  Google Scholar 

  16. Hofmann, T. et al. Direct activation of human TRP6 and TRP3 channels by diacylglycerol. Nature 397, 259–263 (1999).

    CAS  PubMed  Google Scholar 

  17. Hofmann, T., Schaefer, M., Schultz, G. & Gudermann, T. Transient receptor potential channels as molecular substrates of receptor-mediated cation entry. J. Mol. Med. 78, 14–25 (2000).

    CAS  PubMed  Google Scholar 

  18. Harteneck, C., Plant, T. D. & Schultz, G. From worm to man: three subfamilies of TRP channels. Trends Neurosci. 23, 159–166 (2000).

    CAS  PubMed  Google Scholar 

  19. Montell, C. & Rubin, G. M. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2, 1313–1323 (1989).

    CAS  PubMed  Google Scholar 

  20. Clapham, D. E., Runnels, L. W. & Strubing, C. The trp ion channel family. Nature Rev. Neurosci. 2, 387–396 (2001).

    CAS  Google Scholar 

  21. Zitt, C., Halaszovich, C. R. & Luckhoff, A. The TRP family of cation channels: probing and advancing the concepts on receptor-activated calcium entry. Prog. Neurobiol. 66, 243–264 (2002).

    CAS  PubMed  Google Scholar 

  22. Montell, C. Physiology, phylogeny, and functions of the TRP superfamily of cation channels. Sci. STKE [online] (cited 10 July 2001) 〈http://stke.sciencemag.org/cgi/content/full/sigtrans;2001/90/re1〉 (2001).

  23. Montell, C., Birnbaumer, L. & Flockerzi, V. The TRP channels, a remarkably functional family. Cell 108, 595–598 (2002).

    CAS  PubMed  Google Scholar 

  24. Randriamanpita, C. & Tsien, R. Y. Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx. Nature 364, 809–813 (1993).

    Google Scholar 

  25. Thomas, D. & Hanley, M. R. Evaluation of calcium influx factors from stimulated jurkat T-lymphocytes by microinjection into Xenopus oocytes. J. Biol. Chem. 270, 6429–6432 (1995).

    CAS  PubMed  Google Scholar 

  26. Csutora, P. et al. Calcium influx factor is synthesized by yeast and mammalian cells depleted of organellar calcium stores. Proc. Natl Acad. Sci. USA 96, 121–126 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Trepakova, E. S. et al. Calcium influx factor directly activates store-operated cation channels in vascular smooth muscle cells. J. Biol. Chem. 275, 26158–26163 (2000).

    CAS  PubMed  Google Scholar 

  28. Rzigalinski, B. A., Willoughby, K. A., Hoffman, S. W., Falck, J. R. & Ellis, E. F. Calcium influx factor, further evidence it is 5,6-epoxyeicosatrienoic acid. J. Biol. Chem. 274, 175–182 (1999).

    CAS  PubMed  Google Scholar 

  29. Su, Z. et al. A store-operated nonselective cation channel in lymphocytes is activated directly by Ca2+ influx factor and diacylglycerol. Am. J. Physiol. Cell Physiol. 280, C1284–C1292 (2001).

    CAS  PubMed  Google Scholar 

  30. Xie, Q., Zhang, Y., Zhai, C. & Bonanno, J. A. Calcium influx factor from cytochrome P-450 metabolism and secretion-like coupling mechanisms for capacitative calcium entry in corneal endothelial cells. J. Biol. Chem. 277, 16559–16566 (2002).

    CAS  PubMed  Google Scholar 

  31. Glitsch, M. D., Bakowski, D. & Parekh, A. B. Effects of inhibitors of the lipo-oxygenase family of enzymes on the store-operated calcium current I(CRAC) in rat basophilic leukaemia cells. J. Physiol. 539, 93–106 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Irvine, R. F. 'Quantal' Ca2+ release and the control of Ca2+ entry by inositol phosphates — a possible mechanism. FEBS Lett. 263, 5–9 (1990).

    CAS  PubMed  Google Scholar 

  33. Patterson, R. L., van Rossum, D. B. & Gill, D. L. Store operated Ca2+ entry: evidence for a secretion-like coupling model. Cell 98, 487–499 (1999).

    CAS  PubMed  Google Scholar 

  34. Yao, Y., Ferrer-Montiel, A. V., Montal, M., & Tsien, R. Y. Activation of store-operated Ca2+ current in Xenopus oocytes requires SNAP-25 but not a diffusible messenger. Cell 98, 475–485 (1999).

    CAS  PubMed  Google Scholar 

  35. Putney, J. W. “Kissin' cousins”: intimate plasma membrane–ER interactions underlie capacitative calcium entry. Cell 99, 5–8 (1999).

    CAS  PubMed  Google Scholar 

  36. Zweifach, A. & Lewis, R. S. Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ store. Proc. Natl Acad. Sci. USA 90, 6295–6299 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Hoth, M. & Penner, R. Calcium release-activated calcium current in rat mast cells. J. Physiol. (Lond.) 465, 359–386 (1993).

    CAS  Google Scholar 

  38. Hoth, M. & Penner, R. Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature 355, 353–356 (1992).

    CAS  PubMed  Google Scholar 

  39. Zweifach, A. & Lewis, R. S. Rapid inactivation of depletion-activated calcium current (ICRAC) due to local calcium feedback. J. Gen. Physiol. 105, 209–226 (1995).

    CAS  PubMed  Google Scholar 

  40. Kerschbaum, H. H. & Cahalan, M. D. Single-channel recording of a store-operated Ca2+ channel in Jurkat T lymphocytes. Science 283, 836–839 (1999).

    CAS  PubMed  Google Scholar 

  41. Nadler, M. J. et al. LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature 411, 590–595 (2001).

    CAS  PubMed  Google Scholar 

  42. Hermosura, M. C., Monteilh-Zoller, M. K., Scharenberg, A. M., Penner, R., & Fleig, A. Dissociation of the store-operated calcium current I(CRAC) and the Mg-nucleotide-regulated metal ion current MagNuM. J. Physiol 539, 445–458 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Prakriya, M. & Lewis, R. S. Separation and characterization of currents through store-operated CRAC channels and Mg2+-inhibited cation (MIC) channels. J. Gen. Physiol 119, 487–508 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Luckhoff, A. & Clapham, D. E. Calcium channels activated by depletion of internal calcium stores in A431 cells. Biophys. J. 67, 177–182 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Vaca, L. & Kunze, D. L. IP3-activated Ca2+ channels in the plasma membrane of cultured vascular endothelial cells. Am. J. Physiol. 269, C733–C738 (1995).

    CAS  PubMed  Google Scholar 

  46. Krause, E., Pfeiffer, F., Schmid, A. & Schulz, I. Depletion of intracellular calcium stores activates a calcium conducting nonselective cation current in mouse pancreatic acinar cells. J. Biol. Chem. 271, 32523–32528 (1996).

    CAS  PubMed  Google Scholar 

  47. Kiselyov, K. I. et al. Functional interaction between InsP3 receptors and store-operated Htrp3 channels. Nature 396, 478–482 (1998).

    CAS  PubMed  Google Scholar 

  48. Kiselyov, K. I., Mignery, G. A., Zhu, M. X. & Muallem, S. The N-terminal domain of the IP3 receptor gates store-operated hTrp3 channels. Mol. Cell 4, 423–429 (1999).

    CAS  PubMed  Google Scholar 

  49. Boulay, G. et al. Modulation of Ca2+ entry by polypeptides of the inositol 1,4,5-trisphosphate receptor (IP3R) that bind transient receptor potential (TRP): evidence for roles of TRP and IP3R in store depletion-activated Ca2+ entry. Proc. Natl Acad. Sci. USA 96, 14955–14960 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Ma, H.-T. et al. Requirement of the inositol trisphosphate receptor for activation of store-operated Ca2+ channels. Science 287, 1647–1651 (2000).

    CAS  PubMed  Google Scholar 

  51. Berridge, M. J., Lipp, P. & Bootman, M. D. The calcium entry pas de deux. Science 287, 1604–1605 (2000).

    CAS  PubMed  Google Scholar 

  52. Rosado, J. A. & Sage, S. O. Activation of store-mediated calcium entry by secretion-like coupling between the inositol 1,4,5-trisphosphate receptor type II and human transient receptor potential (hTrp1) channels in human platelets. Biochem. J. 356, 191–198 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Rosado, J. A. & Sage, S. O. Coupling between inositol 1,4,5-trisphosphate receptors and human transient receptor potential channel 1 when intracellular Ca2+ stores are depleted. Biochem. J. 350, 631–635 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Zweifach, A. Target-cell contact activates a highly selective capacitative calcium entry pathway in cytotoxic T lymphocytes. J. Cell Biol. 148, 603–614 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Kurosaki, T. et al. Regulation of the phospholipase C-γ2 pathway in B cells. Immunol. Rev. 176, 19–29 (2000).

    CAS  PubMed  Google Scholar 

  56. Hsu, S.-F. et al. Fundamental Ca2+ signaling mechanisms in mouse dendritic cells: CRAC is the major Ca2+ entry pathway. J. Immunol. 166, 6126–6133 (2001).

    CAS  Google Scholar 

  57. Zhang, L. & McCloskey, M. A. Immunoglobulin E receptor-activated calcium conductance in rat mast cells. J. Physiol. (Lond.) 483, 59–66 (1995).

    CAS  Google Scholar 

  58. Gibson, A., McFadzean, I., Wallace, P. & Wayman, C. P. Capacitative Ca2+ entry and the regulation of smooth muscle tone. Trends Pharmacol. Sci. 19, 266–269 (1998).

    CAS  PubMed  Google Scholar 

  59. Dolmetsch, R. E., Xu, K. L. & Lewis, R. S. Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392, 933–936 (1998).

    CAS  PubMed  Google Scholar 

  60. Li, W. H., Llopis, J., Whitney, M., Zlokarnik, G. & Tsien, R. Y. Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression. Nature 392, 936–941 (1998).

    CAS  PubMed  Google Scholar 

  61. Aifantis, I., Gounari, F., Scorrano, L., Borowski, C. & von Boehmer, H. Constitutive pre-TCR signaling promotes differentiation through Ca2+ mobilization and activation of NF-κB and NFAT. Nature Immunol. 2, 403–409 (2001).

    CAS  Google Scholar 

  62. Hunton, D. L. et al. Capacitative calcium entry contributes to nuclear factor of activated T-cells nuclear translocation and hypertrophy in cardiomyocytes. J. Biol. Chem. 277, 14266–14273 (2002).

    CAS  PubMed  Google Scholar 

  63. Golovina, V. A. Cell proliferation is associated with enhanced capacitative Ca2+ entry in human arterial myocytes. Am. J. Physiol 277, C343–C349 (1999).

    CAS  PubMed  Google Scholar 

  64. Jayadev, S. et al. Reduced capacitative calcium entry correlates with vesicle accumulation and apoptosis. J. Biol. Chem. 274, 8261–8268 (1999).

    CAS  PubMed  Google Scholar 

  65. Pinton, P. et al. Reduced loading of intracellular Ca2+ stores and downregulation of capacitative Ca2+ influx in Bcl-2-overexpressing cells. J. Cell Biol. 148, 857–862 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Fagan, K. A., Mahey, R. & Cooper, D. M. F. Functional co-localization of transfected Ca2+-stimulable adenylyl cyclases with capacitative Ca2+ entry sites. J. Biol. Chem. 271, 12438–12444 (1996).

    CAS  PubMed  Google Scholar 

  67. Fagan, K. A., Mons, N. & Cooper, D. M. F. Dependence of the Ca2+-inhibitable adenylyl cyclase of C6-2B glioma cells on capacitative Ca2+ entry. J. Biol. Chem. 273, 9297–9305 (1998).

    CAS  PubMed  Google Scholar 

  68. Kim, Y. H. et al. Phospholipase C-δ1 is activated by capacitative calcium entry that follows phospholipase C-β activation upon bradykinin stimulation. J. Biol. Chem. 274, 26127–26134 (1999).

    CAS  PubMed  Google Scholar 

  69. Lin, S. et al. Sustained endothelial nitric-oxide synthase activation requires capacitative Ca2+ entry. J. Biol. Chem. 275, 17979–17985 (2000).

    CAS  PubMed  Google Scholar 

  70. Mogami, H., Nakano, K., Tepikin, A. V. & Petersen, O. H. Ca2+ flow via tunnels in polarized cells: Recharging of apical Ca2+ by focal Ca2+ entry through basal membrane patch. Cell 88, 49–55 (1997).

    CAS  PubMed  Google Scholar 

  71. Shuttleworth, T. J. What drives calcium entry during [Ca2+]i oscillations? — challenging the capacitative model. Cell Calcium 25, 237–246 (1999).

    CAS  PubMed  Google Scholar 

  72. Corbett, E. F. & Michalak, M. Calcium, a signaling molecule in the endoplasmic reticulum? Trends Biochem. Sci. 25, 307–311 (2000).

    CAS  PubMed  Google Scholar 

  73. Johnson, S., Michalak, M., Opas, M., & Eggleton, P. The ins and outs of calreticulin: from the ER lumen to the extracellular space. Trends Cell Biol. 11, 122–129 (2001).

    CAS  PubMed  Google Scholar 

  74. Short, A. D. et al. Intracellular Ca2+ pool content is linked to cell growth. Proc. Natl Acad. Sci. USA 90, 4986–4990 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Graber, M. N., Alfonso, A., & Gill, D. L. Recovery of Ca2+ pools and growth in Ca2+ pool-depleted cells is mediated by specific epoxyeicosatrienoic acids derived from arachidonic acid. J. Biol. Chem. 272, 29546–29553 (1997).

    CAS  PubMed  Google Scholar 

  76. Mombouli, J. V., Holzmann, S., Kostner, G. M. & Graier, W. F. Potentiation of Ca2+ signaling in endothelial cells by 11,12-epoxyeicosatrienoic acid. J. Cardiovasc. Pharmacol. 33, 779–784 (1999).

    CAS  PubMed  Google Scholar 

  77. Paradiso, A. M., Mason, S. J., Lazarowski, E. R. & Boucher, R. C. Membrane-restricted regulation of Ca2+ release and influx in polarized epithelia. Nature 377, 643–646 (1995).

    CAS  PubMed  Google Scholar 

  78. Petersen, C. C. & Berridge, M. J. Capacitative calcium entry is colocalised with calcium release in Xenopus oocytes: evidence against a highly diffusible calcium influx factor. Pflugers Arch. 432, 286–292 (1996).

    CAS  PubMed  Google Scholar 

  79. Parekh, A. B. & Penner, R. Activation of store-operated calcium influx at resting InsP3 levels by sensitization of the InsP3 receptor in rat basophilic leukaemia cells. J. Physiol. (Lond.) 489, 377–382 (1995).

    CAS  Google Scholar 

  80. McDonald, T. V., Premack, B. A. & Gardner, P. Flash photolysis of caged inositol 1,4,5-trisphosphate activates plasma membrane calcium current in human T cells. J. Biol. Chem. 268, 3889–3896 (1993).

    CAS  PubMed  Google Scholar 

  81. Hofer, A. M., Fasolato, C. & Pozzan, T. Capacitative Ca2+ entry is closely linked to the filling state of internal Ca2+ stores: A study using simultaneous measurements of ICRAC and intraluminal [Ca2+]. J. Cell Biol. 140, 325–334 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Huang, Y. & Putney, J. W. Relationship between intracellular calcium store depletion and calcium release-activated calcium current in a mast cell line (RBL-1). J. Biol. Chem. 273, 19554–19559 (1998).

    CAS  PubMed  Google Scholar 

  83. Ma, H.-T., Favre, C. J., Patterson, R. L., Stone, M. R. & Gill, D. L. Ca2+ entry activated by S-nitrosylation. Relationship to store-operated Ca2+ entry. J. Biol. Chem. 274, 35318–35324 (1999).

    CAS  PubMed  Google Scholar 

  84. Fasolato, C., Hoth, M. & Penner, R. A GTP-dependent step in the activation mechanism of capacitative calcium influx. J. Biol. Chem. 268, 20737–20740 (1993).

    CAS  PubMed  Google Scholar 

  85. Bird, G. S. & Putney, J. W. Inhibition of thapsigargin-induced calcium entry by microinjected guanide nucleotide analogues. Evidence for the involvement of a small G-protein in capacitative calcium entry. J. Biol. Chem. 268, 21486–21488 (1993).

    CAS  PubMed  Google Scholar 

  86. Fernando, K. C., Gregory, R. B., Katsis, F., Kemp, B. E. & Barritt, G. J. Evidence that a low-molecular-mass GTP-binding protein is required for store-activated Ca2+ inflow in hepatocytes. Biochem. J. 328, 463–471 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Blaustein, M. P. & Golovina, V. A. Structural complexity and functional diversity of endoplasmic reticulum Ca2+ stores. Trends Neurosci. 24, 602–608 (2001).

    CAS  PubMed  Google Scholar 

  88. Rosado, J. A., Jenner, S. & Sage, S. O. A role for the actin cytoskeleton in the initiation and maintenance of store-mediated calcium entry in human platelets. Evidence for conformational coupling. J. Biol. Chem. 275, 7527–7533 (2000).

    CAS  PubMed  Google Scholar 

  89. Wang, Y. J., Gregory, R. B. & Barritt, G. J. Regulation of F-actin and endoplasmic reticulum organization by the trimeric G-protein Gi2 in rat hepatocytes. Implication for the activation of store-operated Ca2+ inflow. J. Biol. Chem. 275, 22229–22237 (2000).

    CAS  PubMed  Google Scholar 

  90. Wu, S. et al. Essential control of an endothelial cell ISOC by the spectrin membrane skeleton. J. Cell Biol. 154, 1225–1233 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Bakowski, D., Glitsch, M. D. & Parekh, A. B. An examination of the secretion-like coupling model for the activation of the Ca2+ release-activated Ca2+ current ICRAC in RBL-1 cells. J. Physiol 532, 55–71 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Montell, C. Visual transduction in Drosophila. Annu. Rev. Cell Dev. Biol. 15, 231–268 (1999).

    CAS  PubMed  Google Scholar 

  93. Li, H. S. & Montell, C. TRP and the PDZ protein, INAD, form the core complex required for retention of the signalplex in Drosophila photoreceptor cells. J. Cell Biol. 150, 1411–1422 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Isshiki, M. & Anderson, R. G. Calcium signal transduction from caveolae. Cell Calcium 26, 201–208 (1999).

    CAS  PubMed  Google Scholar 

  95. Lockwich, T. P. et al. Assembly of trp1 in a signaling complex associated with caveolin — scaffolding lipid raft domains. J. Biol. Chem. 275, 11934–11942 (2000).

    CAS  PubMed  Google Scholar 

  96. Smith, K. E., Gu, C., Fagan, K. A., Hu, B. & Cooper, D. M. Residence of adenylyl cyclase type 8 in caveolae is necessary but not sufficient for regulation by capacitative Ca2+ entry. J. Biol. Chem. 277, 6025–6031 (2002).

    CAS  PubMed  Google Scholar 

  97. Valtorta, F., Meldolesi, J. & Fesce, R. Synaptic vesicles: is kissing a matter of competence? Trends Cell Biol. 11, 324–328 (2001).

    CAS  PubMed  Google Scholar 

  98. Barritt, G. J. Does a decrease in subplasmalemmal Ca2+ explain how store-operated Ca2+ channels are opened? Cell Calcium 23, 65–75 (1998).

    CAS  PubMed  Google Scholar 

  99. Cooper, D. M. Calcium-sensitive adenylyl cyclase–aequorin chimeras as sensitive probes for discrete modes of elevation of cytosolic calcium. Methods Enzymol. 345, 105–112 (2002).

    PubMed  Google Scholar 

  100. Montell, C. TRP trapped in fly signaling web. Curr. Opin. Neurobiol. 8, 397 (1998).

    Google Scholar 

  101. Zhu, X., Chu, P. B., Peyton, M. & Birnbaumer, L. Molecular-Cloning of A Widely Expressed Human Homolog for the Drosophila Trp Gene. FEBS Lett. 373, 193–198 (1995).

    CAS  PubMed  Google Scholar 

  102. Wes, P. D. et al. TRPC1, a human homologue of a Drosophila store-operated channel. Proc. Natl Acad. Sci. USA 9652–9656 (1995).

  103. Zhu, X. et al. trp, a novel mammalian gene family essential for agonist-activated capacitative Ca2+ entry. Cell 85, 661–671 (1996).

    CAS  PubMed  Google Scholar 

  104. Montell, C. et al. A unified nomenclature for the superfamily of TRP cation channels. Mol. Cell 9, 229–231 (2002).

    CAS  PubMed  Google Scholar 

  105. Zitt, C. et al. Cloning and functional expression of a human Ca2+ -permeable cation channel activated by calcium store depletion. Neuron 16, 1189–1196 (1996).

    CAS  PubMed  Google Scholar 

  106. Liu, X. et al. Trp1, a candidate protein for the store-operated Ca2+ influx mechanism in salivary gland cells. J. Biol. Chem. 275, 3403–3411 (2000).

    CAS  PubMed  Google Scholar 

  107. Singh, B. B., Liu, X. & Ambudkar, I. S. Expression of truncated transient receptor potential protein 1α (Trp1α). Evidence that the trp1 C terminus modulates store-operated Ca2+ entry. J. Biol. Chem. 275, 36483–36486 (2000).

    CAS  PubMed  Google Scholar 

  108. Vannier, B. et al. Mouse trp2, the homologue of the human trpc2 pseudogene, encodes mTrp2, a store depletion-activated capacitative Ca2+ entry channel. Proc. Natl Acad. Sci. USA 96, 2060–2064 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Vazquez, G., Lievremont, J. P., St J. Bird, G. & Putney, J. W. Jr. Human Trp3 forms both inositol trisphosphate receptor-dependent and receptor-independent store-operated cation channels in DT40 avian B lymphocytes. Proc. Natl Acad. Sci.USA 98, 11777–11782 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Thyagarajan, B. et al. Expression of Trp3 determines sensitivity of capacitative Ca2+ entry to nitric oxide and mitochondrial Ca2+ handling: evidence for a role of Trp3 as a subunit of capacitative Ca2+ entry channels. J. Biol. Chem. 276, 48149–48158 (2001).

    CAS  PubMed  Google Scholar 

  111. Warnat, J., Philipp, S., Zimmer, S., Flockerzi, V. & Cavalie, A. Phenotype of a recombinant store-operated channel: highly selective permeation of Ca2+. J. Physiol. (Lond.) 518, 631–638 (1999).

    CAS  Google Scholar 

  112. Kinoshita, M., Akaike, A., Satoh, M. & Kaneko, S. Positive regulation of capacitative Ca2+ entry by intracellular Ca2+ in Xenopus oocytes expressing rat TRP4. Cell Calcium 28, 151–159 (2000).

    CAS  PubMed  Google Scholar 

  113. Philipp, S. et al. A novel capacitative calcium entry channel expressed in excitable cells. EMBO J. 17, 4274–4282 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Mizuno, N. et al. Molecular cloning and characterization of rat trp homologues from brain. Brain Res. Mol. Brain Res. 64, 41–51 (1999).

    CAS  PubMed  Google Scholar 

  115. Riccio, A. et al. Cloning and functional expression of human short TRP7, a candidate protein for store-operated Ca2+ influx. J. Biol. Chem. 277, 12302–12309 (2002).

    CAS  PubMed  Google Scholar 

  116. Singh, B. B. et al. Trp1-dependent enhancement of salivary gland fluid secretion: role of store-operated calcium entry. FASEB J. 15, 1652–1654 (2001).

    CAS  PubMed  Google Scholar 

  117. Philipp, S. et al. TRP4(CCE1)is part of native Ca2+ release-activated Ca2+-like channels in adrenal cells. J. Biol. Chem. 275, 23965–23972 (2000).

    CAS  PubMed  Google Scholar 

  118. Wu, X., Babnigg, G. & Villereal, M. L. Functional significance of human trp1 and trp3 in store-operated Ca2+ entry in HEK-293 cells. Am. J. Physiol. 278, C526–C536 (2000).

    CAS  Google Scholar 

  119. Gailly, P. & Colson-van Schoor, M. Involvement of trp-2 protein in store-operated influx of calcium in fibroblasts. Cell Calcium 30, 157–165 (2001).

    CAS  PubMed  Google Scholar 

  120. Brough, G. H. et al. Contribution of endogenously expressed Trp1 to a Ca2+-selective, store-operated Ca2+ entry pathway. FASEB J. 15, 1727–1738 (2001).

    CAS  Google Scholar 

  121. Golovina, V. A. et al. Upregulated TRP and enhanced capacitative Ca2+ entry in human pulmonary artery myocytes during proliferation. Am. J. Physiol. Heart Circ. Physiol. 280, H746–H755 (2001).

    CAS  PubMed  Google Scholar 

  122. Freichel, M. et al. Lack of an endothelial store-operated Ca2+ current impairs agonist-dependent vasorelaxation in TRP4−/− mice. Nature Cell Biol. 3, 121–127 (2001).

    CAS  PubMed  Google Scholar 

  123. Mori, Y. et al. Transient receptor potential 1 regulates capacitative Ca2+ entry and Ca2+ release from endoplasmic reticulum in B lymphocytes. J. Exp. Med. 195, 673–681 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Groschner, K. et al. Trp proteins form store-operated cation channels in human vascular endothelial cells [published erratum appears in FEBS Lett. 442, 122 (1999)]. FEBS Lett. 437, 101–106 (1998).

    CAS  PubMed  Google Scholar 

  125. Sinkins, W. G., Estacion, M. & Schilling, W. P. Functional expression of TrpC1: a human homologue of the Drosophila Trp channel. Biochem. J. 331, 331–339 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Zitt, C. et al. Expression of TRPC3 in Chinese hamster ovary cells results in calcium-activated cation currents not related to store depletion. J. Cell Biol. 138, 1333–1341 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Zhu, X., Jiang, M. & Birnbaumer, L. Receptor-activated Ca2+ influx via Trp3 stably expressed in human embryonic kidney (HEK) 293 cells: Evidence for a non-capacitative Ca2+ entry. J. Biol. Chem. 273, 133–142 (1998).

    CAS  PubMed  Google Scholar 

  128. van Rossum, D. B., Patterson, R. L., Ma, H.-T. & Gill, D. L. Ca2+ entry mediated by store-depletion, S-nitrosylation, and TRP3 channels: Comparison of coupling and function. J. Biol. Chem. 275, 28562–28568 (2000).

    CAS  PubMed  Google Scholar 

  129. Venkatachalam, K., Ma, H. T., Ford, D. L. & Gill, D. L. Expression of functional receptor-coupled TRPC3 channels in DT40 triple InsP3 receptor-knockout cells. J. Biol. Chem. 276, 33980–33985 (2001).

    CAS  PubMed  Google Scholar 

  130. Schaefer, M. et al. Receptor-mediated regulation of the nonselective cation channels TRPC4 and TRPC5. J. Biol. Chem. 275, 17517–17526 (2000).

    CAS  PubMed  Google Scholar 

  131. McKay, R. R. et al. Cloning and expression of the human transient receptor potential 4 (TRP4) gene: localization and functional expression of human TRP4 and TRP3. Biochem. J. 351, 735–746 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Obukhov, A. G. & Nowycky, M. C. TRPC4 can be activated by G-protein-coupled receptors and provides sufficient Ca2+ to trigger exocytosis in neuroendocrine cells. J. Biol. Chem. 277, 16172–16178 (2002).

    CAS  PubMed  Google Scholar 

  133. Okada, T. et al. Molecular cloning and functional characterization of a novel receptor-activated TRP Ca2+ channel from mouse brain. J. Biol. Chem. 273, 10279–10287 (1998).

    CAS  PubMed  Google Scholar 

  134. Kanki, H. et al. Activation of inositol 1,4,5-trisphosphate receptor is essential for the opening of mouse TRP5 channels. Mol. Pharmacol. 60, 989–998 (2001).

    CAS  PubMed  Google Scholar 

  135. Boulay, G. et al. Cloning and expression of a novel mammalian homolog of Drosophilia Transient Receptor Potential (TRP) involved in calcium entry secondary to activation of receptors coupled by the Gq class of G protein. J. Biol. Chem. 272, 29672–29680 (1997).

    CAS  PubMed  Google Scholar 

  136. Inoue, R. et al. The transient receptor potential protein homologue TRP6 is the essential component of vascular α(1)-adrenoceptor-activated Ca2+-permeable cation channel. Circ. Res. 88, 325–332 (2001).

    CAS  PubMed  Google Scholar 

  137. Okada, T. et al. Molecular and functional characterization of a novel mouse transient receptor potential protein homologue TRP7. Ca2+-permeable cation channel that is constitutively activated and enhanced by stimulation of G protein-coupled receptor. J. Biol. Chem. 274, 27359–27370 (1999).

    CAS  PubMed  Google Scholar 

  138. Wu, X., Babnigg, G., Zagranichnaya, T. & Villereal, M. L. The role of endogenous human Trp4 in regulating carbachol-induced calcium oscillations in HEK-293 cells. J. Biol. Chem. 277, 13597–13608 (2002).

    CAS  PubMed  Google Scholar 

  139. Stowers, L., Holy, T. E., Meister, M., Dulac, C. & Koentges, G. Loss of sex discrimination and male–male aggression in mice deficient for TRP2. Science 295, 1493–1500 (2002).

    CAS  PubMed  Google Scholar 

  140. Li, H.-S., Xu, X.-Z. S. & Montell, C. Activation of a TRPC3-dependent cation current through the neurotrophin BDNF. Neuron 24, 261–273 (1999).

    CAS  PubMed  Google Scholar 

  141. Liman, E. R., Corey, D. P. & Dulac, C. TRP2: a candidate transduction channel for mammalian pheromone sensory signaling. Proc. Natl Acad. Sci. USA 96, 5791–5796 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Jungnickel, M. K., Marrero, H., Birnbaumer, L., Lemos, J. R. & Florman, H. M. Trp2 regulates entry of Ca2+ into mouse sperm triggered by egg ZP3. Nature Cell Biol. 3, 499–502 (2001).

    CAS  PubMed  Google Scholar 

  143. Xu, X. Z., Li, H. S., Guggino, W. B. & Montell, C. Coassembly of TRP and TRPL produces a distinct store-operated conductance. Cell 89, 1155–1164 (1997).

    CAS  PubMed  Google Scholar 

  144. Strubing, C., Krapivinsky, G., Krapivinsky, L. & Clapham, D. E. TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29, 645–655 (2001).

    CAS  PubMed  Google Scholar 

  145. Lintschinger, B. et al. Coassembly of trp1 and trp3 proteins generates diacylglycerol- and Ca2+- sensitive cation channels. J. Biol. Chem. 275, 27799–27805 (2000).

    CAS  PubMed  Google Scholar 

  146. Hofmann, T., Schaefer, M., Schultz, G. & Gudermann, T. Subunit composition of mammalian transient receptor potential channels in living cells. Proc. Natl Acad. Sci. USA 99, 7461–7466 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Ohki, G. et al. A calcium-activated cation current by an alternatively spliced form of Trp3 in the heart. J. Biol. Chem. 275, 39055–39060 (2000).

    CAS  PubMed  Google Scholar 

  148. Estacion, M., Sinkins, W. G. & Schilling, W. P. Stimulation of Drosophila TrpL by capacitative Ca2+ entry. Biochem. J. 341, 41–49 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Gunthorpe, M. J., Benham, C. D., Randall, A. & Davis, J. B. The diversity in the vanilloid (TRPV) receptor family of ion channels. Trends Pharmacol. Sci. 23, 183–191 (2002).

    CAS  PubMed  Google Scholar 

  150. Yue, L., Peng, J. B., Hediger, M. A. & Clapham, D. E. CaT1 manifests the pore properties of the calcium-release-activated calcium channel. Nature 410, 705–709 (2001).

    CAS  PubMed  Google Scholar 

  151. Voets, T. et al. CaT1 and the calcium release-activated calcium channel manifest distinct pore properties. J. Biol. Chem. 276, 47767–47770 (2001).

    CAS  PubMed  Google Scholar 

  152. Ma, H.-T. et al. Assessment of the role of the inositol 1,4,5-trisphosphate receptor in the activation of transient receptor potential channels and store-operated Ca2+ Entry Channels. J. Biol. Chem. 276, 18888–18896 (2001).

    CAS  PubMed  Google Scholar 

  153. Ma, H. T., Venkatachalam, K., Parys, J. B. & Gill, D. L. Modification of store-operated channel coupling and inositol trisphosphate receptor function by 2-aminoethoxydiphenyl borate in DT40 lymphocytes. J. Biol. Chem. 277, 6915–6922 (2002).

    CAS  PubMed  Google Scholar 

  154. Prakriya, M. & Lewis, R. S. Potentiation and inhibition of Ca2+ release-activated Ca2+ channels by 2-aminoethyldiphenyl borate (2-APB) occurs independently of IP3 receptors. J. Physiol. 536, 3–19 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Schindl, R., Kahr, H., Graz, I., Groschner, K. & Romanin, C. Store-depletion activated CaT1 currents in RBL mast cells are inhibited by 2-APB: Evidence for a regulatory component that controls activation of both CaT1 and CRAC channels. J. Biol. Chem. (2002).

  156. Runnels, L. W., Yue, L. & Clapham, D. E. TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science 291, 1043–1047 (2001).

    CAS  PubMed  Google Scholar 

  157. Runnels, L. W., Yue, L. & Clapham, D. E. The TRPM7 channel is inactivated by PIP2 hydrolysis. Nature Cell Biol. 4, 329–336 (2002).

    CAS  PubMed  Google Scholar 

  158. Zhang, L. & Saffen, D. Muscarinic acetylcholine receptor regulation of TRP6 Ca2+ channel isoforms. Molecular structures and functional characterization. J. Biol. Chem. 276, 13331–13339 (2001).

    CAS  PubMed  Google Scholar 

  159. Estacion, M., Sinkins, W. G. & Schilling, W. P. Regulation of Drosophila transient receptor potential-like (TrpL) channels by phospholipase C-dependent mechanisms. J. Physiol 530, 1–19 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Chyb, S., Raghu, P. & Hardie, R. C. Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL. Nature 397, 255–259 (1999).

    CAS  PubMed  Google Scholar 

  161. Tang, Y. et al. Association of mammalian trp4 and phospholipase C isozymes with a PDZ domain-containing protein, NHERF. J. Biol. Chem. 275, 37559–37564 (2000).

    CAS  PubMed  Google Scholar 

  162. Suh, P. G., Hwang, J. I., Ryu, S. H., Donowitz, M. & Kim, J. H. The roles of PDZ-containing proteins in PLC-beta-mediated signaling. Biochem. Biophys. Res. Commun. 288, 1–7 (2001).

    CAS  PubMed  Google Scholar 

  163. Kuno, M. & Gardner, P. Ion Channels Activated by Inositol 1,4,5-Trisphosphate in Plasma-Membrane of Human Lymphocytes-T. Nature 326, 301–304 (1987).

    CAS  PubMed  Google Scholar 

  164. Kiselyov, K. I., Semyonova, S. B., Mamin, A. G. & Mozhayeva, G. N. Miniature Ca2+ channels in excised plasma-membrane patches: activation by IP3 . Pflugers Arch. 437, 305–314 (1999).

    CAS  PubMed  Google Scholar 

  165. Tang, J. et al. Identification of common binding sites for calmodulin and IP3 receptors on the carboxyl-termini of Trp channels. J. Biol. Chem. 276, 21303–21310 (2001).

    CAS  PubMed  Google Scholar 

  166. Zhang, Z. et al. Activation of Trp3 by inositol 1,4,5-trisphosphate receptors through displacement of inhibitory calmodulin from a common binding domain. Proc. Natl Acad. Sci.USA 98, 3168–3173 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Mery, L., Magnino, F., Schmidt, K., Krause, K. H. & Dufour, J. F. Alternative splice variants of hTrp4 differentially interact with the C-terminal portion of the inositol 1,4,5-trisphosphate receptors. FEBS Lett. 487, 377–383 (2001).

    CAS  PubMed  Google Scholar 

  168. Sugawara, H., Kurosaki, M., Takata, M. & Kurosaki, T. Genetic evidence for involvement of type 1, type 2 and type 3 inositol 1,4,5-trisphosphate receptors in signal transduction through the B-cell antigen receptor. EMBO J. 16, 3078–3088 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  169. Broad, L. M. et al. Role of the phospholipase c-inositol 1,4,5-trisphosphate pathway in calcium release-activated calcium current and capacitative calcium entry. J. Biol. Chem. 276, 15945–15952 (2001).

    CAS  PubMed  Google Scholar 

  170. Acharya, J. K., Jalink, K., Hardy, R. W., Hartenstein, V. & Zuker, C. S. InsP3 receptor is essential for growth and differentiation but not for vision in Drosophila. Neuron 18, 881–887 (1997).

    CAS  PubMed  Google Scholar 

  171. Raghu, P. et al. Constitutive activity of the light-sensitive channels TRP and TRPL in the Drosophila diacylglycerol kinase mutant, rdgA. Neuron 26, 169–179 (2000).

    CAS  PubMed  Google Scholar 

  172. Kiselyov, K. I. et al. Gating of store-operated channels by conformational coupling to ryanodine receptors. Mol. Cell 6, 421–431 (2000).

    CAS  PubMed  Google Scholar 

  173. Kiselyov, K., Shin, D. M., Shcheynikov, N., Kurosaki, T. & Muallem, S. Regulation of Ca2+-release-activated Ca2+ current (Icrac) by ryanodine receptors in inositol 1,4,5-trisphosphate-receptor-deficient DT40 cells. Biochem. J. 360, 17–22 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Kedei, N. et al. Analysis of the native quaternary structure of vanilloid receptor 1. J. Biol. Chem. 276, 28613–28619 (2001).

    CAS  PubMed  Google Scholar 

  175. Xu, X. Z., Chien, F., Butler, A., Salkoff, L. & Montell, C. TRPγ, a Drosophila TRP-related subunit, forms a regulated cation channel with TRPL. Neuron 26, 647–657 (2000).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are most grateful to M. Berridge, J. Putney, C. Montell, D. Clapham, R. Penner, S. Muallem, R. Lewis and D. Cooper for information and helpful discussions.

Author information

Author notes

  1. Randen L. Patterson

    Present address: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, 21201, MD, USA

    Kartik Venkatachalam, Damian B. van Rossum, Hong-Tao Ma & Donald L. Gill

Authors
  1. Kartik Venkatachalam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Damian B. van Rossum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Randen L. Patterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hong-Tao Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Donald L. Gill
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Donald L. Gill.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Venkatachalam, K., van Rossum, D., Patterson, R. et al. The cellular and molecular basis of store-operated calcium entry. Nat Cell Biol 4, E263–E272 (2002). https://doi.org/10.1038/ncb1102-e263

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1102-e263

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing