New Aspects of the Contribution of ER to SOCE Regulation: The Role of the ER and ER-Plasma Membrane Junctions in the Regulation of SOCE

  • Hayley DingsdaleEmail author
  • Emmanuel Okeke
  • Lee Haynes
  • Gyorgy Lur
  • Alexei V. TepikinEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 993)


The junctions between the endoplasmic reticulum and the plasma membrane are essential platforms for the activation of store-operated Ca2+ influx. These junctions have specific dimensions and are nonuniformly distributed in polarized cells. The mechanisms involved in the formation of the junctions are currently undergoing vigorous investigation, and significant progress was attained in this research area during the last 10 years. Some cell types display stationary junctions, while in other cells, new junctions can form rapidly following cytosolic Ca2+ signals and/or the reduction of the Ca2+ concentration in the lumen of the endoplasmic reticulum; furthermore, in moving cells, junctions can undergo saltatory formation, long distance sliding, and dissolution. The proteins involved in the activation of the Ca2+ influx could be also involved in the formation of the junctions. The architecture, dynamics, and localization of the junctions are important for the regulation of Ca2+ signaling cascades and their downstream events.


Store-operated Ca2+ entry ER-PM junctions Ca2+ influx Ca2+ signaling STIM Orai 


  1. Alonso MT, Manjarres IM, Garcia-Sancho J (2012) Privileged coupling between Ca2+ entry through plasma membrane store-operated Ca2+ channels and the endoplasmic reticulum Ca2+ pump. Mol Cell Endocrinol 353:37–44PubMedCrossRefGoogle Scholar
  2. Baba Y, Hayashi K, Fujii Y, Mizushima A, Watarai H, Wakamori M, Numaga T, Mori Y, Iino M, Hikida M, Kurosaki T (2006) Coupling of STIM1 to store-operated Ca2+ entry through its constitutive and inducible movement in the endoplasmic reticulum. Proc Natl Acad Sci U S A 103:16704–16709PubMedPubMedCentralCrossRefGoogle Scholar
  3. Barrow SL, Voronina SG, da Silva Xavier G, Chvanov MA, Longbottom RE, Gerasimenko OV, Petersen OH, Rutter GA, Tepikin AV (2008) ATP depletion inhibits Ca2+ release, influx and extrusion in pancreatic acinar cells but not pathological Ca2+ responses induced by bile. Pflugers Arch 455:1025–1039PubMedCrossRefGoogle Scholar
  4. Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK (2011) Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476:341–345PubMedPubMedCentralCrossRefGoogle Scholar
  5. Berridge MJ (1993) Inositol trisphosphate and calcium signalling. Nature 361:315–325PubMedCrossRefGoogle Scholar
  6. Berridge MJ (1995) Capacitative calcium entry. Biochem J 312(Pt 1):1–11PubMedPubMedCentralCrossRefGoogle Scholar
  7. Berridge MJ (2009) Inositol trisphosphate and calcium signalling mechanisms. Biochim Biophys Acta 1793:933–940PubMedCrossRefGoogle Scholar
  8. Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1:11–21PubMedCrossRefGoogle Scholar
  9. Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4:517–529PubMedCrossRefGoogle Scholar
  10. Bers DM (2002) Cardiac excitation-contraction coupling. Nature 415:198–205PubMedCrossRefGoogle Scholar
  11. Bird GS, Putney JW Jr (2005) Capacitative calcium entry supports calcium oscillations in human embryonic kidney cells. J Physiol 562:697–706PubMedCrossRefGoogle Scholar
  12. Blaustein MP, Lederer WJ (1999) Sodium/calcium exchange: its physiological implications. Physiol Rev 79:763–854PubMedGoogle Scholar
  13. Bogeski I, Kummerow C, Al-Ansary D, Schwarz EC, Koehler R, Kozai D, Takahashi N, Peinelt C, Griesemer D, Bozem M, Mori Y, Hoth M, Niemeyer BA (2010) Differential redox regulation of ORAI ion channels: a mechanism to tune cellular calcium signaling. Sci Signal 3:24CrossRefGoogle Scholar
  14. Bolender RP (1974) Stereological analysis of the guinea pig pancreas. I. Analytical model and quantitative description of nonstimulated pancreatic exocrine cells. J Cell Biol 61:269–287PubMedPubMedCentralCrossRefGoogle Scholar
  15. Borgese N, Francolini M, Snapp E (2006) Endoplasmic reticulum architecture: structures in flux. Curr Opin Cell Biol 18:358–364PubMedPubMedCentralCrossRefGoogle Scholar
  16. Brandt PW, Reuben JP, Girardier L, Grundfest H (1965) Correlated morphological and physiological studies on isolated single muscle fibers. I. Fine structure of the crayfish muscle fiber. J Cell Biol 25(Suppl):233–260PubMedCentralCrossRefGoogle Scholar
  17. Broad LM, Braun FJ, Lievremont JP, Bird GS, Kurosaki T, Putney JW Jr (2001) Role of the phospholipase C-inositol 1,4,5-trisphosphate pathway in calcium release-activated calcium current and capacitative calcium entry. J Biol Chem 276:15945–15952PubMedCrossRefGoogle Scholar
  18. Burdakov D, Petersen OH, Verkhratsky A (2005) Intraluminal calcium as a primary regulator of endoplasmic reticulum function. Cell Calcium 38:303–310PubMedCrossRefGoogle Scholar
  19. Cahalan MD (2009) STIMulating store-operated Ca2+ entry. Nat Cell Biol 11:669–677PubMedPubMedCentralCrossRefGoogle Scholar
  20. Camello P, Gardner J, Petersen OH, Tepikin AV (1996) Calcium dependence of calcium extrusion and calcium uptake in mouse pancreatic acinar cells. J Physiol 490(Pt 3):585–593PubMedPubMedCentralCrossRefGoogle Scholar
  21. Carafoli E (2002) Calcium signaling: a tale for all seasons. Proc Natl Acad Sci U S A 99:1115–1122PubMedPubMedCentralCrossRefGoogle Scholar
  22. Carrasco S, Meyer T (2011) STIM proteins and the endoplasmic reticulum-plasma membrane junctions. Annu Rev Biochem 80:973–1000PubMedPubMedCentralCrossRefGoogle Scholar
  23. Chang CL, Liou J (2015) Phosphatidylinositol 4,5-bisphosphate homeostasis regulated by Nir2 and Nir3 proteins at endoplasmic reticulum-plasma membrane junctions. J Biol Chem 290:14289–14301PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chang CL, Hsieh TS, Yang TT, Rothberg KG, Azizoglu DB, Volk E, Liao JC, Liou J (2013) Feedback regulation of receptor-induced Ca2+ signaling mediated by E-Syt1 and Nir2 at endoplasmic reticulum-plasma membrane junctions. Cell Rep 5:813–825PubMedCrossRefGoogle Scholar
  25. Chung J, Torta F, Masai K, Lucast L, Czapla H, Tanner LB, Narayanaswamy P, Wenk MR, Nakatsu F, De Camilli P (2015) INTRACELLULAR TRANSPORT. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts. Science 349:428–432PubMedPubMedCentralCrossRefGoogle Scholar
  26. Collins SR, Meyer T (2011) Evolutionary origins of STIM1 and STIM2 within ancient Ca2+ signaling systems. Trends Cell Biol 21:202–211PubMedPubMedCentralCrossRefGoogle Scholar
  27. Copeland DE, Dalton AJ (1959) An association between mitochondria and the endoplasmic reticulum in cells of the pseudobranch gland of a teleost. J Biophys Biochem Cytol 5:393–396PubMedPubMedCentralCrossRefGoogle Scholar
  28. Csordas G, Renken C, Varnai P, Walter L, Weaver D, Buttle KF, Balla T, Mannella CA, Hajnoczky G (2006) Structural and functional features and significance of the physical linkage between ER and mitochondria. J Cell Biol 174:915–921PubMedPubMedCentralCrossRefGoogle Scholar
  29. Csordas G, Varnai P, Golenar T, Roy S, Purkins G, Schneider TG, Balla T, Hajnoczky G (2010) Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface. Mol Cell 39:121–132PubMedPubMedCentralCrossRefGoogle Scholar
  30. Csordas G, Golenar T, Seifert EL, Kamer KJ, Sancak Y, Perocchi F, Moffat C, Weaver D, Perez SD, Bogorad R, Koteliansky V, Adijanto J, Mootha VK, Hajnoczky GR (2013) MICU1 controls both the threshold and cooperative activation of the mitochondrial Ca2+ uniporter. Cell Metab 17:976–987PubMedPubMedCentralCrossRefGoogle Scholar
  31. Deak AT, Blass S, Khan MJ, Groschner LN, Waldeck-Weiermair M, Hallstrom S, Graier WF, Malli R (2014) IP3-mediated STIM1 oligomerization requires intact mitochondrial Ca2+ uptake. J Cell Sci 127:2944–2955PubMedPubMedCentralCrossRefGoogle Scholar
  32. De Stefani D, Raffaello A, Teardo E, Szabo I, Rizzuto R (2011) A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476:336–340PubMedPubMedCentralCrossRefGoogle Scholar
  33. De Stefani D, Patron M, Rizzuto R (2015) Structure and function of the mitochondrial calcium uniporter complex. Biochim Biophys Acta 1853:2006–2011PubMedPubMedCentralCrossRefGoogle Scholar
  34. Di Leva F, Domi T, Fedrizzi L, Lim D, Carafoli E (2008) The plasma membrane Ca2+ ATPase of animal cells: structure, function and regulation. Arch Biochem Biophys 476:65–74PubMedCrossRefGoogle Scholar
  35. Dingsdale H, Okeke E, Awais M, Haynes L, Criddle DN, Sutton R, Tepikin AV (2013) Saltatory formation, sliding and dissolution of ER-PM junctions in migrating cancer cells. Biochem J 451:25–32PubMedPubMedCentralCrossRefGoogle Scholar
  36. Dolmetsch RE, Xu KL, Lewis RS (1998) Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392:933–936PubMedCrossRefGoogle Scholar
  37. Eden ER, White IJ, Tsapara A, Futter CE (2010) Membrane contacts between endosomes and ER provide sites for PTP1B-epidermal growth factor receptor interaction. Nat Cell Biol 12:267–272PubMedGoogle Scholar
  38. Eisenberg BR, Eisenberg RS (1982) The T-SR junction in contracting single skeletal muscle fibers. J Gen Physiol 79:1–19PubMedCrossRefGoogle Scholar
  39. English AR, Zurek N, Voeltz GK (2009) Peripheral ER structure and function. Curr Opin Cell Biol 21:596–602PubMedPubMedCentralCrossRefGoogle Scholar
  40. Engstrom H (1958) On the double innervation of the sensory epithelia of the inner ear. Acta Otolaryngol 49:109–118PubMedCrossRefGoogle Scholar
  41. Fameli N, Ogunbayo OA, van Breemen C, Evans AM (2014) Cytoplasmic nanojunctions between lysosomes and sarcoplasmic reticulum are required for specific calcium signaling. F1000Res 3:93PubMedPubMedCentralGoogle Scholar
  42. Fawcett DW, Revel JP (1961) The sarcoplasmic reticulum of a fast-acting fish muscle. J Biophys Biochem Cytol 10(4, Suppl):89–109PubMedPubMedCentralCrossRefGoogle Scholar
  43. Fernandez-Busnadiego R, Saheki Y, De Camilli P (2015) Three-dimensional architecture of extended synaptotagmin-mediated endoplasmic reticulum-plasma membrane contact sites. Proc Natl Acad Sci U S A 112:E2004–E2013PubMedPubMedCentralCrossRefGoogle Scholar
  44. Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel S, Tanasa B, Hogan P, Lewis RS, Daly M, Rao A (2006) A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441:179–185PubMedCrossRefGoogle Scholar
  45. Fill M, Copello JA (2002) Ryanodine receptor calcium release channels. Physiol Rev 82:893–922PubMedCrossRefGoogle Scholar
  46. Franzini-Armstron C (1974) Freeze fracture of skeletal muscle from the Tarantula spider. Structural differentiations of sarcoplasmic reticulum and transverse tubular system membranes. J Cell Biol 61:501–513PubMedCrossRefGoogle Scholar
  47. Friedman JR, Webster BM, Mastronarde DN, Verhey KJ, Voeltz GK (2010) ER sliding dynamics and ER-mitochondrial contacts occur on acetylated microtubules. J Cell Biol 190:363–375PubMedPubMedCentralCrossRefGoogle Scholar
  48. Galione A, White A, Willmott N, Turner M, Potter BV, Watson SP (1993) cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis. Nature 365:456–459PubMedCrossRefGoogle Scholar
  49. Gardiner DM, Grey RD (1983) Membrane junctions in Xenopus eggs: their distribution suggests a role in calcium regulation. J Cell Biol 96:1159–1163PubMedPubMedCentralCrossRefGoogle Scholar
  50. Gatta AT, Wong LH, Sere YY, Calderon-Norena DM, Cockcroft S, Menon AK, Levine TP (2015) A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport. eLife 4:e07253PubMedCentralCrossRefGoogle Scholar
  51. Giordano F, Saheki Y, Idevall-Hagren O, Colombo SF, Pirruccello M, Milosevic I, Gracheva EO, Bagriantsev SN, Borgese N, De Camilli P (2013) PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by the extended synaptotagmins. Cell 153:1494–1509PubMedPubMedCentralCrossRefGoogle Scholar
  52. Grigoriev I, Gouveia SM, van der Vaart B, Demmers J, Smyth JT, Honnappa S, Splinter D, Steinmetz MO, Putney JW Jr, Hoogenraad CC, Akhmanova A (2008) STIM1 is a MT-plus-end-tracking protein involved in remodeling of the ER. Curr Biol 18:177–182PubMedPubMedCentralCrossRefGoogle Scholar
  53. Groenendyk J, Michalak M (2005) Endoplasmic reticulum quality control and apoptosis. Acta Biochim Pol 52:381–395PubMedGoogle Scholar
  54. Gwack Y, Srikanth S, Feske S, Cruz-Guilloty F, Oh-hora M, Neems D, Hogan P, Rao A (2007) Biochemical and functional characterization of Orai proteins. J Biol Chem 282:16232–16243PubMedCrossRefGoogle Scholar
  55. Henne WM, Zhu L, Balogi Z, Stefan C, Pleiss JA, Emr SD (2015) Mdm1/Snx13 is a novel ER-endolysosomal interorganelle tethering protein. J Cell Biol 210:541–551PubMedPubMedCentralCrossRefGoogle Scholar
  56. Hetzer MW, Walther TC, Mattaj IW (2005) Pushing the envelope: structure, function, and dynamics of the nuclear periphery. Annu Rev Cell Dev Biol 21:347–380PubMedCrossRefGoogle Scholar
  57. Holthuis JC, Levine TP (2005) Lipid traffic: floppy drives and a superhighway. Nat Rev Mol Cell Biol 6:209–220PubMedCrossRefGoogle Scholar
  58. Hoth M, Niemeyer BA (2013) The neglected CRAC proteins: Orai2, Orai3, and STIM2. Curr Top Membr 71:237–271PubMedCrossRefGoogle Scholar
  59. Hoth M, Fanger CM, Lewis RS (1997) Mitochondrial regulation of store-operated calcium signaling in T lymphocytes. J Cell Biol 137:633–648PubMedPubMedCentralCrossRefGoogle Scholar
  60. Idevall-Hagren O, Lu A, Xie B, De Camilli P (2015) Triggered Ca2+ influx is required for extended synaptotagmin 1-induced ER-plasma membrane tethering. EMBO J 34:2291–2305PubMedPubMedCentralCrossRefGoogle Scholar
  61. Irvine RF (1990) Quantal Ca2+ release and the control of Ca2+ entry by inositol phosphates—a possible mechanism. FEBS Lett 263:5–9PubMedCrossRefGoogle Scholar
  62. Jamieson JD, Palade GE (1967) Intracellular transport of secretory proteins in the pancreatic exocrine cell. I. Role of the peripheral elements of the Golgi complex. J Cell Biol 34:577–596PubMedPubMedCentralCrossRefGoogle Scholar
  63. Jousset H, Frieden M, Demaurex N (2007) STIM1 knockdown reveals that store-operated Ca2+ channels located close to sarco/endoplasmic Ca2+ ATPases (SERCA) pumps silently refill the endoplasmic reticulum. J Biol Chem 282:11456–11464PubMedCrossRefGoogle Scholar
  64. Kamer KJ, Mootha VK (2014) MICU1 and MICU2 play nonredundant roles in the regulation of the mitochondrial calcium uniporter. EMBO Rep 15:299–307PubMedPubMedCentralCrossRefGoogle Scholar
  65. Kamer KJ, Mootha VK (2015) The molecular era of the mitochondrial calcium uniporter. Nat Rev Mol Cell Biol 16:545–553PubMedCrossRefGoogle Scholar
  66. Kar P, Parekh AB (2015) Distinct spatial Ca2+ signatures selectively activate different NFAT transcription factor isoforms. Mol Cell 58:232–243PubMedPubMedCentralCrossRefGoogle Scholar
  67. Kar P, Nelson C, Parekh AB (2011) Selective activation of the transcription factor NFAT1 by calcium microdomains near Ca2+ release-activated Ca2+ (CRAC) channels. J Biol Chem 286:14795–14803PubMedPubMedCentralCrossRefGoogle Scholar
  68. Kar P, Samanta K, Kramer H, Morris O, Bakowski D, Parekh AB (2014) Dynamic assembly of a membrane signaling complex enables selective activation of NFAT by Orai1. Curr Biol 24:1361–1368PubMedPubMedCentralCrossRefGoogle Scholar
  69. Kilpatrick BS, Eden ER, Schapira AH, Futter CE, Patel S (2013) Direct mobilisation of lysosomal Ca2+ triggers complex Ca2+ signals. J Cell Sci 126:60–66PubMedCrossRefGoogle Scholar
  70. Kim YJ, Guzman-Hernandez ML, Wisniewski E, Balla T (2015) Phosphatidylinositol-phosphatidic acid exchange by Nir2 at ER-PM contact sites maintains phosphoinositide signaling competence. Dev Cell 33:549–561PubMedPubMedCentralCrossRefGoogle Scholar
  71. Krapivinsky G, Krapivinsky L, Stotz SC, Manasian Y, Clapham DE (2011) POST, partner of stromal interaction molecule 1 (STIM1), targets STIM1 to multiple transporters. Proc Natl Acad Sci U S A 108:19234–19239PubMedPubMedCentralCrossRefGoogle Scholar
  72. Lavieu G, Orci L, Shi L, Geiling M, Ravazzola M, Wieland F, Cosson P, Rothman JE (2010) Induction of cortical endoplasmic reticulum by dimerization of a coatomer-binding peptide anchored to endoplasmic reticulum membranes. Proc Natl Acad Sci U S A 107:6876–6881PubMedPubMedCentralCrossRefGoogle Scholar
  73. Lee HC (2011) Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling. Sci China Life Sci 54:699–711PubMedCrossRefGoogle Scholar
  74. Lee MC, Miller EA, Goldberg J, Orci L, Schekman R (2004) Bi-directional protein transport between the ER and Golgi. Annu Rev Cell Dev Biol 20:87–123PubMedCrossRefGoogle Scholar
  75. Lee KP, Yuan JP, Hong JH, So I, Worley PF, Muallem S (2010) An endoplasmic reticulum/plasma membrane junction: STIM1/Orai1/TRPCs. FEBS Lett 584:2022–2027PubMedCrossRefGoogle Scholar
  76. Lefkimmiatis K, Srikanthan M, Maiellaro I, Moyer M, Curci S, Hofer AM (2009) Store-operated cyclic AMP signalling mediated by STIM1. Nat Cell Biol 11:433–442PubMedCrossRefGoogle Scholar
  77. Levine T, Loewen C (2006) Inter-organelle membrane contact sites: through a glass, darkly. Curr Opin Cell Biol 18:371–378PubMedCrossRefGoogle Scholar
  78. Lewis RS (2007) The molecular choreography of a store-operated calcium channel. Nature 446:284–287PubMedCrossRefGoogle Scholar
  79. Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE, Meyer T (2005) STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol 15:1235–1241PubMedPubMedCentralCrossRefGoogle Scholar
  80. Liou J, Fivaz M, Inoue T, Meyer T (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 U S A 104:9301–9306PubMedPubMedCentralCrossRefGoogle Scholar
  81. Loewen CJ, Young BP, Tavassoli S, Levine TP (2007) Inheritance of cortical ER in yeast is required for normal septin organization. J Cell Biol 179:467–483PubMedPubMedCentralCrossRefGoogle Scholar
  82. Luik R, Wu MM, Buchanan J, Lewis RS (2006) The elementary unit of store-operated Ca2+ entry: local activation of CRAC channels by STIM1 at ER-plasma membrane junctions. J Cell Biol 174:815–825PubMedPubMedCentralCrossRefGoogle Scholar
  83. Luik RM, Wang B, Prakriya M, Wu MM, Lewis RS (2008) Oligomerization of STIM1 couples ER calcium depletion to CRAC channel activation. Nature 454:538–542PubMedPubMedCentralCrossRefGoogle Scholar
  84. Lur G, Haynes LP, Prior IA, Gerasimenko OV, Feske S, Petersen OH, Burgoyne RD, Tepikin AV (2009) Ribosome-free terminals of rough ER allow formation of STIM1 puncta and segregation of STIM1 from IP(3) receptors. Curr Biol 19:1648–1653PubMedPubMedCentralCrossRefGoogle Scholar
  85. Maiellaro I, Lefkimmiatis K, Moyer MP, Curci S, Hofer AM (2012) Termination and activation of store-operated cyclic AMP production. J Cell Mol Med 16:2715–2725PubMedPubMedCentralCrossRefGoogle Scholar
  86. Maleth J, Choi S, Muallem S, Ahuja M (2014) Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating. Nat Commun 5:5843PubMedPubMedCentralCrossRefGoogle Scholar
  87. Manford AG, Stefan CJ, Yuan HL, Macgurn JA, Emr SD (2012) ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology. Dev Cell 23:1129–1140PubMedCrossRefGoogle Scholar
  88. Manjarres IM, Rodriguez-Garcia A, Alonso MT, Garcia-Sancho J (2010) The sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) is the third element in capacitative calcium entry. Cell Calcium 47:412–418PubMedCrossRefGoogle Scholar
  89. Manjarres IM, Alonso MT, Garcia-Sancho J (2011) Calcium entry-calcium refilling (CECR) coupling between store-operated Ca2+ entry and sarco/endoplasmic reticulum Ca2+-ATPase. Cell Calcium 49:153–161PubMedCrossRefGoogle Scholar
  90. Mercer JC, Dehaven WI, Smyth JT, Wedel B, Boyles RR, Bird GS, Putney JW Jr (2006) Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1. J Biol Chem 281:24979–24990PubMedPubMedCentralCrossRefGoogle Scholar
  91. Michalak M, Robert Parker JM, Opas M (2002) Ca2+ signaling and calcium binding chaperones of the endoplasmic reticulum. Cell Calcium 32:269–278PubMedCrossRefGoogle Scholar
  92. Mogami H, Nakano K, Tepikin AV, Petersen OH (1997) Ca2+ flow via tunnels in polarized cells: recharging of apical Ca2+ stores by focal Ca2+ entry through basal membrane patch. Cell 88:49–55PubMedCrossRefGoogle Scholar
  93. Montalvo GB, Artalejo AR, Gilabert JA (2006) ATP from subplasmalemmal mitochondria controls Ca2+ dependent inactivation of CRAC channels. J Biol Chem 281:35616–35623PubMedCrossRefGoogle Scholar
  94. Moser von Filseck J, Copic A, Delfosse V, Vanni S, Jackson CL, Bourguet W, Drin G (2015) INTRACELLULAR TRANSPORT. Phosphatidylserine transport by ORP/Osh proteins is driven by phosphatidylinositol 4-phosphate. Science 349:432–436PubMedCrossRefGoogle Scholar
  95. Naghdi S, Waldeck-Weiermair M, Fertschai I, Poteser M, Graier WF, Malli R (2010) Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1-Orai1-dependent store-operated Ca2+ entry. J Cell Sci 123:2553–2564PubMedCrossRefGoogle Scholar
  96. Nunes P, Demaurex N (2014) Redox regulation of store-operated Ca2+ entry. Antioxid Redox Signal 21:915–932PubMedPubMedCentralCrossRefGoogle Scholar
  97. Nunes P, Cornut D, Bochet V, Hasler U, Oh-Hora M, Waldburger JM, Demaurex N (2012) STIM1 juxtaposes ER to phagosomes, generating Ca(2)(+) hotspots that boost phagocytosis. Curr Biol 22:1990–1997PubMedCrossRefGoogle Scholar
  98. Okeke E, Dingsdale H, Parker T, Voronina S, Tepikin AV (2016a) Endoplasmic reticulum-plasma membrane junctions: structure, function and dynamics. J Physiol 594:2837–2847PubMedPubMedCentralCrossRefGoogle Scholar
  99. Okeke E, Parker T, Dingsdale H, Concannon M, Awais M, Voronina S, Molgo J, Begg M, Metcalf D, Knight AE, Sutton R, Haynes L, Tepikin AV (2016b) Epithelial-mesenchymal transition, IP3 receptors and ER-PM junctions: translocation of Ca2+ signalling complexes and regulation of migration. Biochem J 473:757–767PubMedPubMedCentralCrossRefGoogle Scholar
  100. Orci L, Ravazzola M, Le Coadic M, Shen W, Demaurex N, Cosson P (2009) STIM1-induced precortical and cortical subdomains of the endoplasmic reticulum. Proc Natl Acad Sci U S A 106:19358–19362PubMedPubMedCentralCrossRefGoogle Scholar
  101. Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4:552–565PubMedCrossRefGoogle Scholar
  102. Palade GE (1955) A small particulate component of the cytoplasm. J Biophys Biochem Cytol 1:59–68PubMedPubMedCentralCrossRefGoogle Scholar
  103. Palty R, Raveh A, Kaminsky I, Meller R, Reuveny E (2012) SARAF inactivates the store operated calcium entry machinery to prevent excess calcium refilling. Cell 149:425–438PubMedCrossRefGoogle Scholar
  104. Parekh AB (2003) Mitochondrial regulation of intracellular Ca2+ signaling: more than just simple Ca2+ buffers. News Physiol Sci 18:252–256PubMedGoogle Scholar
  105. Parekh AB (2008) Mitochondrial regulation of store-operated CRAC channels. Cell Calcium 44:6–13PubMedCrossRefGoogle Scholar
  106. Parekh AB (2011) Decoding cytosolic Ca2+ oscillations. Trends Biochem Sci 36:78–87PubMedCrossRefGoogle Scholar
  107. Parekh AB, Muallem S (2011) Ca(2+) signalling and gene regulation. Cell Calcium 49:279PubMedCrossRefGoogle Scholar
  108. Park MK, Petersen OH, Tepikin AV (2000) The endoplasmic reticulum as one continuous Ca(2+) pool: visualization of rapid Ca(2+) movements and equilibration. EMBO J 19:5729–5739PubMedPubMedCentralCrossRefGoogle Scholar
  109. Park C, Hoover P, Mullins F, Bachhawat P, Covington E, Raunser S, Walz T, Garcia K, Dolmetsch R, Lewis RS (2009) STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell 136:876–890PubMedPubMedCentralCrossRefGoogle Scholar
  110. Patron M, Checchetto V, Raffaello A, Teardo E, Reane DV, Mantoan M, Granatiero V, Szabo I, De Stefani D, Rizzuto R (2014) MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol Cell 53:726–737PubMedPubMedCentralCrossRefGoogle Scholar
  111. Patterson RL, van Rossum DB, Gill DL (1999) Store-operated Ca2+ entry: evidence for a secretion-like coupling model. Cell 98:487–499PubMedCrossRefGoogle Scholar
  112. Perocchi F, Gohil VM, Girgis HS, Bao XR, McCombs JE, Palmer AE, Mootha VK (2010) MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake. Nature 467:291–296PubMedPubMedCentralCrossRefGoogle Scholar
  113. Petersen OH, Tepikin AV (2008) Polarized calcium signaling in exocrine gland cells. Annu Rev Physiol 70:273–299PubMedCrossRefGoogle Scholar
  114. Porter KR, Palade GE (1957) Studies on the endoplasmic reticulum. III. Its form and distribution in striated muscle cells. J Biophys Biochem Cytol 3:269–300PubMedPubMedCentralCrossRefGoogle Scholar
  115. Prakriya M, Lewis RS (2001) Potentiation and inhibition of Ca(2+) release-activated Ca(2+) channels by 2-aminoethyldiphenyl borate (2-APB) occurs independently of IP(3) receptors. J Physiol 536:3–19PubMedPubMedCentralCrossRefGoogle Scholar
  116. Prakriya M, Feske S, Gwack Y, Srikanth S, Rao A, Hogan PG (2006) Orai1 is an essential pore subunit of the CRAC channel. Nature 443:230–233PubMedCrossRefGoogle Scholar
  117. Prinz WA (2014) Bridging the gap: membrane contact sites in signaling, metabolism, and organelle dynamics. J Cell Biol 205:759–769PubMedPubMedCentralCrossRefGoogle Scholar
  118. Putney JW Jr (1986) A model for receptor-regulated calcium entry. Cell Calcium 7:1–12PubMedCrossRefGoogle Scholar
  119. Putney JW Jr (2007) Recent breakthroughs in the molecular mechanism of capacitative calcium entry (with thoughts on how we got here). Cell Calcium 42:103–110PubMedPubMedCentralCrossRefGoogle Scholar
  120. Putney JW Jr, Bird GS (2008) Cytoplasmic calcium oscillations and store-operated calcium influx. J Physiol 586:3055–3059PubMedPubMedCentralCrossRefGoogle Scholar
  121. Reger JF (1961) The fine structure of neuromuscular junctions and the sarcoplasmic reticulum of extrinsic eye muscles of Fundulus heteroclitus. J Biophys Biochem Cytol 10(4, Suppl):111–121PubMedPubMedCentralCrossRefGoogle Scholar
  122. Ritchie MF, Samakai E, Soboloff J (2012) STIM1 is required for attenuation of PMCA-mediated Ca2+ clearance during T-cell activation. EMBO J 31:1123–1133PubMedPubMedCentralCrossRefGoogle Scholar
  123. Rizzuto RR, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T (1998) Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280:1763–1766PubMedCrossRefGoogle Scholar
  124. Roos J, DiGregorio P, Yeromin A, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak J, Wagner S, Cahalan M, Velicelebi G, Stauderman K (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169:435–445PubMedPubMedCentralCrossRefGoogle Scholar
  125. Rosado JA, Lopez JJ, Harper AG, Harper MT, Redondo PC, Pariente JA, Sage SO, Salido GM (2004) Two pathways for store-mediated calcium entry differentially dependent on the actin cytoskeleton in human platelets. J Biol Chem 279:29231–29235PubMedCrossRefGoogle Scholar
  126. Rosenbluth J (1962) Subsurface cisterns and their relationship to the neuronal plasma membrane. J Cell Biol 13:405–421PubMedPubMedCentralCrossRefGoogle Scholar
  127. Rossi AE, Dirksen RT (2006) Sarcoplasmic reticulum: the dynamic calcium governor of muscle. Muscle Nerve 33:715–731PubMedCrossRefGoogle Scholar
  128. Rutkowski DT, Kaufman RJ (2004) A trip to the ER: coping with stress. Trends Cell Biol 14:20–28PubMedCrossRefGoogle Scholar
  129. Schulz TA, Choi MG, Raychaudhuri S, Mears JA, Ghirlando R, Hinshaw JE, Prinz WA (2009) Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologues. J Cell Biol 187:889–903PubMedPubMedCentralCrossRefGoogle Scholar
  130. Sharma S, Quintana A, Findlay GM, Mettlen M, Baust B, Jain M, Nilsson R, Rao A, Hogan PG (2013) An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry. Nature 499:238–242PubMedCrossRefGoogle Scholar
  131. Singaravelu K, Nelson C, Bakowski D, de Brito OM, Ng SW, Di Capite J, Powell T, Scorrano L, Parekh AB (2011) Mitofusin 2 regulates STIM1 migration from the Ca2+ store to the plasma membrane in cells with depolarized mitochondria. J Biol Chem 286:12189–12201PubMedPubMedCentralCrossRefGoogle Scholar
  132. Smyth J, DeHaven W, Bird G, Putney JW Jr (2008) Ca2+-store-dependent and independent reversal of Stim1 localization and function. J Cell Sci 121:762–772PubMedPubMedCentralCrossRefGoogle Scholar
  133. Smyth JT, Petranka JG, Boyles RR, Dehaven WI, Fukushima M, Johnson KL, Williams JG, Putney JW Jr (2009) Phosphorylation of STIM1 underlies suppression of store-operated calcium entry during mitosis. Nat Cell Biol 11:1465–1472PubMedPubMedCentralCrossRefGoogle Scholar
  134. Smyth JT, Beg AM, Wu SL, Putney JW Jr, Rusan NM (2012) Phosphoregulation of STIM1 leads to exclusion of the endoplasmic reticulum from the mitotic spindle. Curr Biol 22:1487–1493PubMedPubMedCentralCrossRefGoogle Scholar
  135. Tabas I, Ron D (2011) Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 13:184–190PubMedPubMedCentralCrossRefGoogle Scholar
  136. Takeshima H, Hoshijima M, Song LS (2015) Ca(2+) microdomains organized by junctophilins. Cell Calcium 58:349–356PubMedPubMedCentralCrossRefGoogle Scholar
  137. Taylor CW, Rahman T, Tovey SC, Dedos SG, Taylor EJ, Velamakanni S (2009) IP3 receptors: some lessons from DT40 cells. Immunol Rev 231:23–44PubMedCrossRefGoogle Scholar
  138. Tepikin AV, Voronina SG, Gallacher DV, Petersen OH (1992) Pulsatile Ca2+ extrusion from single pancreatic acinar-cells during receptor-activated cytosolic Ca2+ spiking. J Biol Chem 267:14073–14076PubMedGoogle Scholar
  139. Tsai FC, Meyer T (2012) Ca2+ pulses control local cycles of Lamellipodia retraction and adhesion along the front of migrating cells. Curr Biol 22:837–842PubMedPubMedCentralCrossRefGoogle Scholar
  140. Tsai FC, Seki A, Yang HW, Hayer A, Carrasco S, Malmersjo S, Meyer T (2014) A polarized Ca2+, diacylglycerol and STIM1 signalling system regulates directed cell migration. Nat Cell Biol 16:133–144PubMedPubMedCentralCrossRefGoogle Scholar
  141. Varnai P, Toth B, Toth DJ, Hunyady L, Balla T (2007) Visualization and manipulation of plasma membrane-endoplasmic reticulum contact sites indicates the presence of additional molecular components within the STIM1-Orai1 complex. J Biol Chem 282:29678–29690PubMedCrossRefGoogle Scholar
  142. Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP (2006) CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science 312:1220–1223PubMedCrossRefGoogle Scholar
  143. Voeltz GK, Rolls MM, Rapoport TA (2002) Structural organization of the endoplasmic reticulum. EMBO Rep 3:944–950PubMedPubMedCentralCrossRefGoogle Scholar
  144. Walsh C, Barrow S, Voronina S, Chvanov M, Petersen OH, Tepikin A (2009) Modulation of calcium signalling by mitochondria. Biochim Biophys Acta 1787:1374–1382PubMedCrossRefGoogle Scholar
  145. Walsh CM, Chvanov M, Haynes LP, Petersen OH, Tepikin AV, Burgoyne RD (2010) Role of phosphoinositides in STIM1 dynamics and store-operated calcium entry. Biochem J 425:159–168CrossRefGoogle Scholar
  146. Watanabe H, Burnstock G (1976) Junctional subsurface organs in frog sympathetic ganglion cells. J Neurocytol 5:125–136PubMedCrossRefGoogle Scholar
  147. Willoughby D, Wachten S, Masada N, Cooper DM (2010) Direct demonstration of discrete Ca2+ microdomains associated with different isoforms of adenylyl cyclase. J Cell Sci 123:107–117PubMedCrossRefGoogle Scholar
  148. Willoughby D, Everett KL, Halls ML, Pacheco J, Skroblin P, Vaca L, Klussmann E, Cooper DM (2012) Direct binding between Orai1 and AC8 mediates dynamic interplay between Ca2+ and cAMP signaling. Sci Signal 5:ra29PubMedCrossRefGoogle Scholar
  149. Wu MM, Buchanan J, Luik RM, Lewis RS (2006) Ca2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane. J Cell Biol 174:803–813PubMedPubMedCentralCrossRefGoogle Scholar
  150. Wu MM, Covington ED, Lewis RS (2014) Single-molecule analysis of diffusion and trapping of STIM1 and Orai1 at endoplasmic reticulum-plasma membrane junctions. Mol Biol Cell 25:3672–3685PubMedPubMedCentralCrossRefGoogle Scholar
  151. Wuytack F, Raeymaekers L, Missiaen L (2002) Molecular physiology of the SERCA and SPCA pumps. Cell Calcium 32:279–305PubMedCrossRefGoogle Scholar
  152. Xu P, Lu J, Li Z, Yu X, Chen L, Xu T (2006) Aggregation of STIM1 underneath the plasma membrane induces clustering of Orai1. Biochem Biophys Res Commun 350:969–976PubMedCrossRefGoogle Scholar
  153. Yu F, Sun L, Machaca K (2010) Constitutive recycling of the store-operated Ca2+ channel Orai1 and its internalization during meiosis. J Cell Biol 191:523–535PubMedPubMedCentralCrossRefGoogle Scholar
  154. Yuan JP, Zeng W, Dorwart MR, Choi YJ, Worley PF, Muallem S (2009) SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat Cell Biol 11:337–343PubMedPubMedCentralCrossRefGoogle Scholar
  155. Zhang SL, Yu Y, Roos J, Kozak JA, Deerinck TJ, Ellisman MH, Stauderman KA, Cahalan MD (2005) STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437:902–905PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.School of BiosciencesCardiff UniversityCardiffUK
  2. 2.The Physiological Laboratory, Department of Cellular and Molecular Physiology, Institute of Translational MedicineThe University of LiverpoolLiverpoolUK
  3. 3.Department of NeurobiologyYale School of MedicineNew HavenUSA

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