Skip to main content
SpringerLink
Log in

The TRPCs, Orais and STIMs in ER/PM Junctions

  • Chapter
  • First Online:
Calcium Entry Pathways in Non-excitable Cells

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 898))

Abstract

The Ca2+ second messenger is initiated at ER/PM junctions and propagates into the cell interior to convey the receptor information. The signal is maintained by Ca2+ influx across the plasma membrane through the Orai and TRPC channels. These Ca2+ influx channels form complexes at ER/PM junctions with the ER Ca2+ sensor STIM1, which activates the channels. The function of STIM1 is modulated by other STIM isoforms like STIM1L, STIM2 and STIM2.1/STIM2β and by SARAF, which mediates the Ca2+-dependent inhibition of Orai channels. The ER/PM junctions are formed at membrane contact sites by tethering proteins that generate several types of ER/PM junctions, such as PI(4,5)P2-poor and PI(4,5)P2-rich domains. This chapter discusses several properties of the TRPC channels, the Orai channels and the STIMs, their key interacting proteins and how interaction of the STIMs with the channels gates their activity. The chapter closes by highlighting open questions and potential future directions in this field.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kiselyov K, Shin DM, Muallem S (2003) Signalling specificity in GPCR-dependent Ca2+ signalling. Cell Signal 15(3):243–253

    Article  CAS  PubMed  Google Scholar 

  2. Galione A (2015) A primer of NAADP-mediated Ca signalling: from sea urchin eggs to mammalian cells. Cell Calcium 58(1):27–47

    Article  CAS  PubMed  Google Scholar 

  3. Pandol SJ, Schoeffield MS, Fimmel CJ, Muallem S (1987) The agonist-sensitive calcium pool in the pancreatic acinar cell. Activation of plasma membrane Ca2+ influx mechanism. J Biol Chem 262(35):16963–16968

    CAS  PubMed  Google Scholar 

  4. Parekh AB, Putney JW Jr (2005) Store-operated calcium channels. Physiol Rev 85(2):757–810

    Article  CAS  PubMed  Google Scholar 

  5. Berridge MJ (2006) Calcium microdomains: organization and function. Cell Calcium 40(5–6):405–412

    Article  CAS  PubMed  Google Scholar 

  6. 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(10):2022–2027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Petersen OH, Sutton R, Criddle DN (2006) Failure of calcium microdomain generation and pathological consequences. Cell Calcium 40(5–6):593–600

    Article  CAS  PubMed  Google Scholar 

  8. Liao Y, Abramowitz J, Birnbaumer L (2014) The TRPC family of TRP channels: roles inferred (mostly) from knockout mice and relationship to ORAI proteins. Handb Exp Pharmacol 223:1055–1075

    Article  CAS  PubMed  Google Scholar 

  9. Smani T, Shapovalov G, Skryma R, Prevarskaya N, Rosado JA (2015) Functional and physiopathological implications of TRP channels. Biochim Biophys Acta 1853(8):1772–1782

    Article  CAS  PubMed  Google Scholar 

  10. de Souza LB, Ambudkar IS (2014) Trafficking mechanisms and regulation of TRPC channels. Cell Calcium 56(2):43–50

    Article  PubMed  CAS  Google Scholar 

  11. Shim AH, Tirado-Lee L, Prakriya M (2015) Structural and functional mechanisms of CRAC channel regulation. J Mol Biol 427(1):77–93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hogan PG, Rao A (2015) Store-operated calcium entry: mechanisms and modulation. Biochem Biophys Res Commun 460(1):40–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Choi S, Maleth J, Jha A, Lee KP, Kim MS, So I, Ahuja M, Muallem S (2014) The TRPCs-STIM1-Orai interaction. Handb Exp Pharmacol 223:1035–1054

    Article  CAS  PubMed  Google Scholar 

  14. Wes PD, Chevesich J, Jeromin A, Rosenberg C, Stetten G, Montell C (1995) TRPC1, a human homolog of a Drosophila store-operated channel. Proc Natl Acad Sci U S A 92(21):9652–9656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhu X, Chu PB, Peyton M, Birnbaumer L (1995) Molecular cloning of a widely expressed human homologue for the Drosophila trp gene. FEBS Lett 373(3):193–198

    Article  CAS  PubMed  Google Scholar 

  16. Gees M, Owsianik G, Nilius B, Voets T (2012) TRP channels. Compr Physiol 2(1):563–608

    PubMed  Google Scholar 

  17. Liao M, Cao E, Julius D, Cheng Y (2013) Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504(7478):107–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cao E, Liao M, Cheng Y, Julius D (2013) TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504(7478):113–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D (2015) Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature 520(7548):511–517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kiselyov K, Shin DM, Kim JY, Yuan JP, Muallem S (2007) TRPC channels: interacting proteins. Handb Exp Pharmacol 179:559–574

    Article  CAS  PubMed  Google Scholar 

  21. Lin Z, Chen Q, Lee M, Cao X, Zhang J, Ma D, Chen L, Hu X, Wang H, Wang X, Zhang P, Liu X, Guan L, Tang Y, Yang H, Tu P, Bu D, Zhu X, Wang K, Li R, Yang Y (2012) Exome sequencing reveals mutations in TRPV3 as a cause of Olmsted syndrome. Am J Hum Genet 90(3):558–564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Loukin S, Su Z, Kung C (2011) Increased basal activity is a key determinant in the severity of human skeletal dysplasia caused by TRPV4 mutations. PLoS ONE 6(5):e19533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chung MK, Guler AD, Caterina MJ (2008) TRPV1 shows dynamic ionic selectivity during agonist stimulation. Nat Neurosci 11(5):555–564

    Article  CAS  PubMed  Google Scholar 

  24. Kim HJ, Yamaguchi S, Li Q, So I, Muallem S (2010) Properties of the TRPML3 channel pore and its stable expansion by the Varitint-Waddler-causing mutation. J Biol Chem 285(22):16513–16520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jeon JP, Roh SE, Wie J, Kim J, Kim H, Lee KP, Yang D, Jeon JH, Cho NH, Kim IG, Kang DE, Kim HJ, So I (2013) Activation of TRPC4beta by Galphai subunit increases Ca2+ selectivity and controls neurite morphogenesis in cultured hippocampal neuron. Cell Calcium 54(4):307–319

    Article  CAS  PubMed  Google Scholar 

  26. Yuan JP, Lee KP, Hong JH, Muallem S (2012) The closing and opening of TRPC channels by Homer1 and STIM1. Acta Physiol 204(2):238–247

    Article  CAS  Google Scholar 

  27. Beneken J, Tu JC, Xiao B, Nuriya M, Yuan JP, Worley PF, Leahy DJ (2000) Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition. Neuron 26(1):143–154

    Article  CAS  PubMed  Google Scholar 

  28. Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S, Worley PF (2003) Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell 114(6):777–789

    Article  CAS  PubMed  Google Scholar 

  29. Lee KP, Yuan JP, So I, Worley PF, Muallem S (2010) STIM1-dependent and STIM1-independent function of transient receptor potential canonical (TRPC) channels tunes their store-operated mode. J Biol Chem 285(49):38666–38673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ong HL, Ambudkar IS (2015) Molecular determinants of TRPC1 regulation within ER-PM junctions. Cell Calcium 58:376–386

    Article  CAS  PubMed  Google Scholar 

  31. Adebiyi A, Narayanan D, Jaggar JH (2011) Caveolin-1 assembles type 1 inositol 1,4,5-trisphosphate receptors and canonical transient receptor potential 3 channels into a functional signaling complex in arterial smooth muscle cells. J Biol Chem 286(6):4341–4348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Freichel M, Tsvilovskyy V, Camacho-Londono JE (2014) TRPC4- and TRPC4-containing channels. Handb Exp Pharmacol 222:85–128

    Article  CAS  PubMed  Google Scholar 

  33. Pani B, Liu X, Bollimuntha S, Cheng KT, Niesman IR, Zheng C, Achen VR, Patel HH, Ambudkar IS, Singh BB (2013) Impairment of TRPC1-STIM1 channel assembly and AQP5 translocation compromise agonist-stimulated fluid secretion in mice lacking caveolin1. J Cell Sci 126(Pt 2):667–675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ong HL, Jang SI, Ambudkar IS (2012) Distinct contributions of Orai1 and TRPC1 to agonist-induced [Ca(2+)](i) signals determine specificity of Ca(2+)-dependent gene expression. PLoS ONE 7(10):e47146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sundivakkam PC, Freichel M, Singh V, Yuan JP, Vogel SM, Flockerzi V, Malik AB, Tiruppathi C (2012) The Ca(2+) sensor stromal interaction molecule 1 (STIM1) is necessary and sufficient for the store-operated Ca(2+) entry function of transient receptor potential canonical (TRPC) 1 and 4 channels in endothelial cells. Mol Pharmacol 81(4):510–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Antigny F, Koenig S, Bernheim L, Frieden M (2013) During post-natal human myogenesis, normal myotube size requires TRPC1- and TRPC4-mediated Ca(2)(+) entry. J Cell Sci 126(Pt 11):2525–2533

    Article  CAS  PubMed  Google Scholar 

  37. Shim S, Zheng JQ, Ming GL (2013) A critical role for STIM1 in filopodial calcium entry and axon guidance. Mol Brain 6:51

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Treves S, Feriotto G, Moccagatta L, Gambari R, Zorzato F (2000) Molecular cloning, expression, functional characterization, chromosomal localization, and gene structure of junctate, a novel integral calcium binding protein of sarco(endo)plasmic reticulum membrane. J Biol Chem 275(50):39555–39568

    Article  CAS  PubMed  Google Scholar 

  39. Treves S, Franzini-Armstrong C, Moccagatta L, Arnoult C, Grasso C, Schrum A, Ducreux S, Zhu MX, Mikoshiba K, Girard T, Smida-Rezgui S, Ronjat M, Zorzato F (2004) Junctate is a key element in calcium entry induced by activation of InsP3 receptors and/or calcium store depletion. J Cell Biol 166(4):537–548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Treves S, Vukcevic M, Griesser J, Armstrong CF, Zhu MX, Zorzato F (2010) Agonist-activated Ca2+ influx occurs at stable plasma membrane and endoplasmic reticulum junctions. J Cell Sci 123(Pt 23):4170–4181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Stamboulian S, Moutin MJ, Treves S, Pochon N, Grunwald D, Zorzato F, De Waard M, Ronjat M, Arnoult C (2005) Junctate, an inositol 1,4,5-triphosphate receptor associated protein, is present in rodent sperm and binds TRPC2 and TRPC5 but not TRPC1 channels. Dev Biol 286(1):326–337

    Article  CAS  PubMed  Google Scholar 

  42. Srikanth S, Jew M, Kim KD, Yee MK, Abramson J, Gwack Y (2012) Junctate is a Ca2 + -sensing structural component of Orai1 and stromal interaction molecule 1 (STIM1). Proc Natl Acad Sci U S A 109(22):8682–8687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Takeshima H, Komazaki S, Nishi M, Iino M, Kangawa K (2000) Junctophilins: a novel family of junctional membrane complex proteins. Mol Cell 6(1):11–22

    CAS  PubMed  Google Scholar 

  44. Takeshima H, Hoshijima M, Song LS (2015) Ca microdomains organized by junctophilins. Cell Calcium 58:349–356

    Article  CAS  PubMed  Google Scholar 

  45. Moriguchi S, Nishi M, Komazaki S, Sakagami H, Miyazaki T, Masumiya H, Saito SY, Watanabe M, Kondo H, Yawo H, Fukunaga K, Takeshima H (2006) Functional uncoupling between Ca2+ release and afterhyperpolarization in mutant hippocampal neurons lacking junctophilins. Proc Natl Acad Sci U S A 103(28):10811–10816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A (2006) A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441(7090):179–185

    Article  CAS  PubMed  Google Scholar 

  47. 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(5777):1220–1223

    Article  CAS  PubMed  Google Scholar 

  48. Zhang SL, Yeromin AV, Zhang XH, Yu Y, Safrina O, Penna A, Roos J, Stauderman KA, Cahalan MD (2006) Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity. Proc Natl Acad Sci U S A 103(24):9357–9362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Stathopulos PB, Ikura M (2013) Structural aspects of calcium-release activated calcium channel function. Channels (Austin) 7(5):344–353

    Article  CAS  Google Scholar 

  50. Hou X, Pedi L, Diver MM, Long SB (2012) Crystal structure of the calcium release-activated calcium channel Orai. Science 338(6112):1308–1313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Demuro A, Penna A, Safrina O, Yeromin AV, Amcheslavsky A, Cahalan MD, Parker I (2011) Subunit stoichiometry of human Orai1 and Orai3 channels in closed and open states. Proc Natl Acad Sci U S A 108(43):17832–17837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Penna A, Demuro A, Yeromin AV, Zhang SL, Safrina O, Parker I, Cahalan MD (2008) The CRAC channel consists of a tetramer formed by stim-induced dimerization of Orai dimers. Nature 456(7218):116–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ji W, Xu P, Li Z, Lu J, Liu L, Zhan Y, Chen Y, Hille B, Xu T, Chen L (2008) Functional stoichiometry of the unitary calcium-release-activated calcium channel. Proc Natl Acad Sci U S A 105(36):13668–13673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. McNally BA, Yamashita M, Engh A, Prakriya M (2009) Structural determinants of ion permeation in CRAC channels. Proc Natl Acad Sci U S A 106(52):22516–22521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Stathopulos PB, Schindl R, Fahrner M, Zheng L, Gasmi-Seabrook GM, Muik M, Romanin C, Ikura M (2013) STIM1/Orai1 coiled-coil interplay in the regulation of store-operated calcium entry. Nat Commun 4:2963

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Palty R, Stanley C, Isacoff EY (2015) Critical role for Orai1 C-terminal domain and TM4 in CRAC channel gating. Cell Res 25:963–980

    Article  CAS  PubMed  Google Scholar 

  57. Tirado-Lee L, Yamashita M, Prakriya M (2015) Conformational changes in the Orai1 C-terminus evoked by STIM1 binding. PLoS ONE 10(6):e0128622

    Article  PubMed  PubMed Central  Google Scholar 

  58. Mignen O, Thompson JL, Shuttleworth TJ (2008) Both Orai1 and Orai3 are essential components of the arachidonate-regulated Ca2 + -selective (ARC) channels. J Physiol 586(1):185–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zhang X, Zhang W, Gonzalez-Cobos JC, Jardin I, Romanin C, Matrougui K, Trebak M (2014) Complex role of STIM1 in the activation of store-independent Orai1/3 channels. J Gen Physiol 143(3):345–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Thompson JL, Mignen O, Shuttleworth TJ (2013) The ARC channel – an endogenous store-independent Orai channel. Curr Top Membr 71:125–148

    Article  CAS  PubMed  Google Scholar 

  61. 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(3):523–535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. 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 5:5843

    Article  PubMed  PubMed Central  Google Scholar 

  63. Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED, Raunser S, Walz T, Garcia KC, Dolmetsch RE, Lewis RS (2009) STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell 136(5):876–890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Liu Y, Zheng X, Mueller GA, Sobhany M, DeRose EF, Zhang Y, London RE, Birnbaumer L (2012) Crystal structure of calmodulin binding domain of orai1 in complex with Ca2+ calmodulin displays a unique binding mode. J Biol Chem 287(51):43030–43041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mullins FM, Park CY, Dolmetsch RE, Lewis RS (2009) STIM1 and calmodulin interact with Orai1 to induce Ca2 + -dependent inactivation of CRAC channels. Proc Natl Acad Sci U S A 106(36):15495–15500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. 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(2):425–438

    Article  CAS  PubMed  Google Scholar 

  67. Jha A, Ahuja M, Maleth J, Moreno CM, Yuan JP, Kim MS, Muallem S (2013) The STIM1 CTID domain determines access of SARAF to SOAR to regulate Orai1 channel function. J Cell Biol 202(1):71–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Srikanth S, Jung HJ, Kim KD, Souda P, Whitelegge J, Gwack Y (2010) A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that stabilizes CRAC channels in T cells. Nat Cell Biol 12(5):436–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Velicelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169(3):435–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr, Meyer T (2005) STIM is a Ca2+ sensor essential for Ca2 + -store-depletion-triggered Ca2+ influx. Curr Biol 15(13):1235–1241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Stathopulos PB, Zheng L, Li GY, Plevin MJ, Ikura M (2008) Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry. Cell 135(1):110–122

    Article  CAS  PubMed  Google Scholar 

  72. Zheng L, Stathopulos PB, Li GY, Ikura M (2008) Biophysical characterization of the EF-hand and SAM domain containing Ca2+ sensory region of STIM1 and STIM2. Biochem Biophys Res Commun 369(1):240–246

    Article  CAS  PubMed  Google Scholar 

  73. Huang GN, Zeng W, Kim JY, Yuan JP, Han L, Muallem S, Worley PF (2006) STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels. Nat Cell Biol 8(9):1003–1010

    Article  CAS  PubMed  Google Scholar 

  74. Fahrner M, Muik M, Schindl R, Butorac C, Stathopulos P, Zheng L, Jardin I, Ikura M, Romanin C (2014) A coiled-coil clamp controls both conformation and clustering of stromal interaction molecule 1 (STIM1). J Biol Chem 289(48):33231–33244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Yu F, Sun L, Hubrack S, Selvaraj S, Machaca K (2013) Intramolecular shielding maintains STIM1 in an inactive conformation. J Cell Sci 126:2401–2410

    Article  CAS  PubMed  Google Scholar 

  76. Yang X, Jin H, Cai X, Li S, Shen Y (2012) Structural and mechanistic insights into the activation of stromal interaction molecule 1 (STIM1). Proc Natl Acad Sci U S A 109(15):5657–5662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 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(3):337–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Feske S, Picard C, Fischer A (2010) Immunodeficiency due to mutations in ORAI1 and STIM1. Clin Immunol 135(2):169–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Miederer AM, Alansary D, Schwar G, Lee PH, Jung M, Helms V, Niemeyer BA (2015) A STIM2 splice variant negatively regulates store-operated calcium entry. Nat Commun 6:6899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Rana A, Yen M, Sadaghiani AM, Malmersjo S, Park CY, Dolmetsch RE, Lewis RS (2015) Alternative splicing converts STIM2 from an activator to an inhibitor of store-operated calcium channels. J Cell Biol 209(5):653–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. 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(22):9301–9306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Korzeniowski MK, Manjarres IM, Varnai P, Balla T (2010) Activation of STIM1-Orai1 involves an intramolecular switching mechanism. Sci Signal 3(148):ra82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Muik M, Fahrner M, Schindl R, Stathopulos P, Frischauf I, Derler I, Plenk P, Lackner B, Groschner K, Ikura M, Romanin C (2011) STIM1 couples to ORAI1 via an intramolecular transition into an extended conformation. EMBO J 30(9):1678–1689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. 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(3):177–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Smyth JT, Beg AM, Wu S, Putney JW Jr, Rusan NM (2012) Phosphoregulation of STIM1 leads to exclusion of the endoplasmic reticulum from the mitotic spindle. Curr Biol 22(16):1487–1493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Pozo-Guisado E, Casas-Rua V, Tomas-Martin P, Lopez-Guerrero AM, Alvarez-Barrientos A, Martin-Romero FJ (2013) Phosphorylation of STIM1 at ERK1/2 target sites regulates interaction with the microtubule plus-end binding protein EB1. J Cell Sci 126(Pt 14):3170–3180

    Article  CAS  PubMed  Google Scholar 

  87. Asanov A, Sherry R, Sampieri A, Vaca L (2013) A relay mechanism between EB1 and APC facilitate STIM1 puncta assembly at endoplasmic reticulum-plasma membrane junctions. Cell Calcium 54(3):246–256

    Article  CAS  PubMed  Google Scholar 

  88. Shinde AV, Motiani RK, Zhang X, Abdullaev IF, Adam AP, Gonzalez-Cobos JC, Zhang W, Matrougui K, Vincent PA, Trebak M (2013) STIM1 controls endothelial barrier function independently of Orai1 and Ca2+ entry. Sci Signal 6(267):ra18

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Hawkins BJ, Irrinki KM, Mallilankaraman K, Lien YC, Wang Y, Bhanumathy CD, Subbiah R, Ritchie MF, Soboloff J, Baba Y, Kurosaki T, Joseph SK, Gill DL, Madesh M (2010) S-glutathionylation activates STIM1 and alters mitochondrial homeostasis. J Cell Biol 190(3):391–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Prins D, Groenendyk J, Touret N, Michalak M (2011) Modulation of STIM1 and capacitative Ca2+ entry by the endoplasmic reticulum luminal oxidoreductase ERp57. EMBO Rep 12(11):1182–1188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Lee KP, Yuan JP, Zeng W, So I, Worley PF, Muallem S (2009) Molecular determinants of fast Ca2 + -dependent inactivation and gating of the Orai channels. Proc Natl Acad Sci U S A 106(34):14687–14692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Derler I, Fahrner M, Muik M, Lackner B, Schindl R, Groschner K, Romanin C (2009) A Ca2(+)release-activated Ca2(+) (CRAC) modulatory domain (CMD) within STIM1 mediates fast Ca2(+)-dependent inactivation of ORAI1 channels. J Biol Chem 284(37):24933–24938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lee KP, Choi S, Hong JH, Ahuja M, Graham S, Ma R, So I, Shin DM, Muallem S, Yuan JP (2014) Molecular determinants mediating gating of transient receptor potential canonical (TRPC) channels by stromal interaction molecule 1 (STIM1). J Biol Chem 289(10):6372–6382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Yuan JP, Zeng W, Huang GN, Worley PF, Muallem S (2007) STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. Nat Cell Biol 9(6):636–645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Liu X, Bandyopadhyay BC, Singh BB, Groschner K, Ambudkar IS (2005) Molecular analysis of a store-operated and 2-acetyl-sn-glycerol-sensitive non-selective cation channel. Heteromeric assembly of TRPC1-TRPC3. J Biol Chem 280(22):21600–21606

    Article  CAS  PubMed  Google Scholar 

  96. Zeng W, Yuan JP, Kim MS, Choi YJ, Huang GN, Worley PF, Muallem S (2008) STIM1 gates TRPC channels, but not Orai1, by electrostatic interaction. Mol Cell 32(3):439–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Muik M, Schindl R, Fahrner M, Romanin C (2012) Ca(2+) release-activated Ca(2+) (CRAC) current, structure, and function. Cell Mol Life Sci 69(24):4163–4176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Cao X, Choi S, Maleth JJ, Park S, Ahuja M, Muallem S (2015) The ER/PM microdomain, PI(4,5)P and the regulation of STIM1-Orai1 channel function. Cell Calcium 58:342–348

    Article  CAS  PubMed  Google Scholar 

  99. Muik M, Frischauf I, Derler I, Fahrner M, Bergsmann J, Eder P, Schindl R, Hesch C, Polzinger B, Fritsch R, Kahr H, Madl J, Gruber H, Groschner K, Romanin C (2008) Dynamic coupling of the putative coiled-coil domain of ORAI1 with STIM1 mediates ORAI1 channel activation. J Biol Chem 283(12):8014–8022

    Article  CAS  PubMed  Google Scholar 

  100. Frischauf I, Muik M, Derler I, Bergsmann J, Fahrner M, Schindl R, Groschner K, Romanin C (2009) Molecular determinants of the coupling between STIM1 and Orai channels: differential activation of Orai1-3 channels by a STIM1 coiled-coil mutant. J Biol Chem 284(32):21696–21706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. McNally BA, Somasundaram A, Jairaman A, Yamashita M, Prakriya M (2013) The C- and N-terminal STIM1 binding sites on Orai1 are required for both trapping and gating CRAC channels. J Physiol 591(Pt 11):2833–2850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. McNally BA, Somasundaram A, Yamashita M, Prakriya M (2012) Gated regulation of CRAC channel ion selectivity by STIM1. Nature 482(7384):241–245

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Lichtenegger M, Groschner K (2014) TRPC3: a multifunctional signaling molecule. Handb Exp Pharmacol 222:67–84

    Article  CAS  PubMed  Google Scholar 

  104. Lis A, Peinelt C, Beck A, Parvez S, Monteilh-Zoller M, Fleig A, Penner R (2007) CRACM1, CRACM2, and CRACM3 are store-operated Ca(2+) channels with distinct functional properties. Curr Biol 17(9):794–800

    Article  CAS  PubMed  Google Scholar 

  105. Darbellay B, Arnaudeau S, Bader CR, Konig S, Bernheim L (2011) STIM1L is a new actin-binding splice variant involved in fast repetitive Ca2+ release. J Cell Biol 194(2):335–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Horinouchi T, Higashi T, Higa T, Terada K, Mai Y, Aoyagi H, Hatate C, Nepal P, Horiguchi M, Harada T, Miwa S (2012) Different binding property of STIM1 and its novel splice variant STIM1L to Orai1, TRPC3, and TRPC6 channels. Biochem Biophys Res Commun 428(2):252–258

    Article  CAS  PubMed  Google Scholar 

  107. Sauc S, Bulla M, Nunes P, Orci L, Marchetti A, Antigny F, Bernheim L, Cosson P, Frieden M, Demaurex N (2015) STIM1L traps and gates Orai1 channels without remodeling the cortical ER. J Cell Sci 128(8):1568–1579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Brandman O, Liou J, Park WS, Meyer T (2007) STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels. Cell 131(7):1327–1339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Ong HL, de Souza LB, Zheng C, Cheng KT, Liu X, Goldsmith CM, Feske S, Ambudkar IS (2015) STIM2 enhances receptor-stimulated Ca(2)(+) signaling by promoting recruitment of STIM1 to the endoplasmic reticulum-plasma membrane junctions. Sci Signal 8(359):ra3

    Article  PubMed  CAS  Google Scholar 

  110. Shalygin A, Skopin A, Kalinina V, Zimina O, Glushankova L, Mozhayeva GN, Kaznacheyeva E (2015) STIM1 and STIM2 proteins differently regulate endogenous store-operated channels in HEK293 cells. J Biol Chem 290(8):4717–4727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Cooper DM (2015) Store-operated Ca-entry and adenylyl cyclase. Cell Calcium 58:368–375

    Article  CAS  PubMed  Google Scholar 

  112. Penny CJ, Kilpatrick BS, Eden ER, Patel S (2015) Coupling acidic organelles with the ER through Ca microdomains at membrane contact sites. Cell Calcium 58:387–396

    Article  CAS  PubMed  Google Scholar 

  113. Raiborg C, Wenzel EM, Stenmark H (2015) ER-endosome contact sites: molecular compositions and functions. EMBO J 34:1848–1858

    Article  CAS  PubMed  Google Scholar 

  114. Lahiri S, Toulmay A, Prinz WA (2015) Membrane contact sites, gateways for lipid homeostasis. Curr Opin Cell Biol 33:82–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Prinz WA (2014) Bridging the gap: membrane contact sites in signaling, metabolism, and organelle dynamics. J Cell Biol 205(6):759–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Kasai H, Augustine GJ (1990) Cytosolic Ca2+ gradients triggering unidirectional fluid secretion from exocrine pancreas. Nature 348(6303):735–738

    Article  CAS  PubMed  Google Scholar 

  117. Thorn P, Lawrie AM, Smith PM, Gallacher DV, Petersen OH (1993) Local and global cytosolic Ca2+ oscillations in exocrine cells evoked by agonists and inositol trisphosphate. Cell 74(4):661–668

    Article  CAS  PubMed  Google Scholar 

  118. Min SW, Chang WP, Sudhof TC (2007) E-Syts, a family of membranous Ca2 + -sensor proteins with multiple C2 domains. Proc Natl Acad Sci U S A 104(10):3823–3828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Toulmay A, Prinz WA (2012) A conserved membrane-binding domain targets proteins to organelle contact sites. J Cell Sci 125(Pt 1):49–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. 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(7):1494–1509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Fischer MA, Temmerman K, Ercan E, Nickel W, Seedorf M (2009) Binding of plasma membrane lipids recruits the yeast integral membrane protein Ist2 to the cortical ER. Traffic 10(8):1084–1097

    Article  CAS  PubMed  Google Scholar 

  122. Jang Y, Oh U (2014) Anoctamin 1 in secretory epithelia. Cell Calcium 55(6):355–361

    Article  CAS  PubMed  Google Scholar 

  123. 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(7457):238–242

    Article  CAS  PubMed  Google Scholar 

  124. Chao JT, Wong AK, Tavassoli S, Young BP, Chruscicki A, Fang NN, Howe LJ, Mayor T, Foster LJ, Loewen CJ (2014) Polarization of the endoplasmic reticulum by ER-septin tethering. Cell 158(3):620–632

    Article  CAS  PubMed  Google Scholar 

  125. Kim S, Kedan A, Marom M, Gavert N, Keinan O, Selitrennik M, Laufman O, Lev S (2013) The phosphatidylinositol-transfer protein Nir2 binds phosphatidic acid and positively regulates phosphoinositide signalling. EMBO Rep 14(10):891–899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. 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(5):549–561

    Article  CAS  PubMed  Google Scholar 

  127. 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(3):813–825

    Article  PubMed  CAS  Google Scholar 

  128. 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(16):E2004–E2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Jean S, Mikryukov A, Tremblay MG, Baril J, Guillou F, Bellenfant S, Moss T (2010) Extended-synaptotagmin-2 mediates FGF receptor endocytosis and ERK activation in vivo. Dev Cell 19(3):426–439

    Article  CAS  PubMed  Google Scholar 

  130. Tremblay MG, Herdman C, Guillou F, Mishra PK, Baril J, Bellenfant S, Moss T (2015) Extended synaptotagmin interaction with the fibroblast growth factor receptor depends on receptor conformation, not catalytic activity. J Biol Chem 290(26):16142–16156

    Article  CAS  PubMed  Google Scholar 

  131. Hong JH, Li Q, Kim MS, Shin DM, Feske S, Birnbaumer L, Cheng KT, Ambudkar IS, Muallem S (2011) Polarized but differential localization and recruitment of STIM1, Orai1 and TRPC channels in secretory cells. Traffic 12(2):232–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Schleifer H, Doleschal B, Lichtenegger M, Oppenrieder R, Derler I, Frischauf I, Glasnov TN, Kappe CO, Romanin C, Groschner K (2012) Novel pyrazole compounds for pharmacological discrimination between receptor-operated and store-operated Ca(2+) entry pathways. Br J Pharmacol 167(8):1712–1722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oral Biology, BK 21 PLUS Project, Yonsei University College of Dentistry, Seoul, 120-752, South Korea

    Dong Min Shin

  2. Epithelial Signaling and Transport Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD, 20892, USA

    Aran Son, Malini Ahuja & Shmuel Muallem

  3. Department of Physiology, School of Medicine, EwhaWomans University, 911-1 Mok-6-dong, Yang Chun-gu, Seoul, 158-710, South Korea

    Seonghee Park

  4. Department of Oral Physiology, School of Dentistry, Wonkwang University, Iksan City, Jeonbuk, South Korea

    Min Seuk Kim

Authors
  1. Dong Min Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aran Son
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seonghee Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Min Seuk Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Malini Ahuja
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shmuel Muallem
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dong Min Shin or Shmuel Muallem .

Editor information

Editors and Affiliations

  1. Depto. Fisiología, University of Extremadura, Cáceres, Spain

    Juan A. Rosado

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Shin, D.M., Son, A., Park, S., Kim, M.S., Ahuja, M., Muallem, S. (2016). The TRPCs, Orais and STIMs in ER/PM Junctions. In: Rosado, J. (eds) Calcium Entry Pathways in Non-excitable Cells. Advances in Experimental Medicine and Biology, vol 898. Springer, Cham. https://doi.org/10.1007/978-3-319-26974-0_3

Download citation

Publish with us

Policies and ethics

Search

Navigation