Physiological Functions of CRAC Channels

Literature Cited

1. 1. 

   Trebak M, Kinet JP. 2019. Calcium signalling in T cells. Nat. Rev. Immunol. 19:154–69
   [Google Scholar]
2. 2. 

   Clapham DE. 2007. Calcium signaling. Cell 131:1047–58
   [Google Scholar]
3. 3. 

   Feske S, Skolnik EY, Prakriya M. 2012. Ion channels and transporters in lymphocyte function and immunity. Nat. Rev. Immunol. 12:532–47
   [Google Scholar]
4. 4. 

   Hogan PG, Rao A. 2015. Store-operated calcium entry: mechanisms and modulation. Biochem. Biophys. Res. Commun. 460:40–49
   [Google Scholar]
5. 5. 

   Prakriya M, Lewis RS. 2015. Store-operated calcium channels. Physiol. Rev. 95:1383–436
   [Google Scholar]
6. 6. 

   Shaw PJ, Feske S. 2012. Regulation of lymphocyte function by ORAI and STIM proteins in infection and autoimmunity. J. Physiol. 590:4157–67
   [Google Scholar]
7. 7. 

   Arruda AP, Hotamisligil GS. 2015. Calcium homeostasis and organelle function in the pathogenesis of obesity and diabetes. Cell Metab. 22:381–97
   [Google Scholar]
8. 8. 

   Zhang I, Hu H. 2020. Store-operated calcium channels in physiological and pathological states of the nervous system. Front. Cell. Neurosci. 14:600758
   [Google Scholar]
9. 9. 

   Putney JW Jr. 1986. A model for receptor-regulated calcium entry. Cell Calcium 7:1–12
   [Google Scholar]
10. 10. 

    Trebak M, Putney JW Jr. 2017. ORAI calcium channels. Physiology 32:332–42
    [Google Scholar]
11. 11. 

    Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED et al. 2009. STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell 136:876–90
    [Google Scholar]
12. 12. 

    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. 11:337–43
    [Google Scholar]
13. 13. 

    Hoth M, Penner R. 1992. Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature 355:353–56
    [Google Scholar]
14. 14. 

    Lewis RS, Cahalan MD. 1989. Mitogen-induced oscillations of cytosolic Ca²⁺ and transmembrane Ca²⁺ current in human leukemic T cells. Cell Regul. 1:99–112
    [Google Scholar]
15. 15. 

    McCarl CA, Picard C, Khalil S, Kawasaki T, Rother J et al. 2009. ORAI1 deficiency and lack of store-operated Ca²⁺ entry cause immunodeficiency, myopathy, and ectodermal dysplasia. J. Allergy Clin. Immunol. 124:1311–18.e7
    [Google Scholar]
16. 16. 

    Lian J, Cuk M, Kahlfuss S, Kozhaya L, Vaeth M et al. 2018. ORAI1 mutations abolishing store-operated Ca²⁺ entry cause anhidrotic ectodermal dysplasia with immunodeficiency. J. Allergy Clin. Immunol. 142:1297–310.e11
    [Google Scholar]
17. 17. 

    Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH et al. 2006. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441:179–85
    [Google Scholar]
18. 18. 

    Picard C, McCarl CA, Papolos A, Khalil S, Lüthy K et al. 2009. STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity. N. Engl. J. Med. 360:1971–80
    [Google Scholar]
19. 19. 

    Vaeth M, Feske S. 2018. Ion channelopathies of the immune system. Curr. Opin. Immunol. 52:39–50
    [Google Scholar]
20. 20. 

    Feske S, Müller JM, Graf D, Kroczek RA, Dräger R et al. 1996. Severe combined immunodeficiency due to defective binding of the nuclear factor of activated T cells in T lymphocytes of two male siblings. Eur. J. Immunol. 26:2119–26
    [Google Scholar]
21. 21. 

    Feske S, Giltnane J, Dolmetsch R, Staudt LM, Rao A. 2001. Gene regulation mediated by calcium signals in T lymphocytes. Nat. Immunol. 2:316–24
    [Google Scholar]
22. 22. 

    Le Deist F, Hivroz C, Partiseti M, Thomas C, Buc HA et al. 1995. A primary T-cell immunodeficiency associated with defective transmembrane calcium influx. Blood 85:1053–62
    [Google Scholar]
23. 23. 

    Liou J, Kim ML, Heo WD, Jones JT, Myers JW et al. 2005. STIM is a Ca²⁺ sensor essential for Ca²⁺-store-depletion-triggered Ca²⁺ influx. Curr. Biol. 15:1235–41
    [Google Scholar]
24. 24. 

    Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M et al. 2005. STIM1, an essential and conserved component of store-operated Ca²⁺ channel function. J. Cell Biol. 169:435–45
    [Google Scholar]
25. 25. 

    Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D et al. 2006. CRACM1 is a plasma membrane protein essential for store-operated Ca²⁺ entry. Science 312:1220–23
    [Google Scholar]
26. 26. 

    Zhang SL, Yeromin AV, Zhang XH, Yu Y, Safrina O et al. 2006. Genome-wide RNAi screen of Ca²⁺ influx identifies genes that regulate Ca²⁺ release-activated Ca²⁺ channel activity. PNAS 103:9357–62
    [Google Scholar]
27. 27. 

    Yoast RE, Emrich SM, Trebak M. 2020. The anatomy of native CRAC channel(s). Curr. Opin. Physiol. 17:89–95
    [Google Scholar]
28. 28. 

    Lacruz RS, Feske S. 2015. Diseases caused by mutations in ORAI1 and STIM1. Ann. N. Y. Acad. Sci. 1356:45–79
    [Google Scholar]
29. 29. 

    Cai X. 2007. Molecular evolution and structural analysis of the Ca²⁺ release-activated Ca²⁺ channel subunit, Orai. J. Mol. Biol. 368:1284–91
    [Google Scholar]
30. 30. 

    Lis A, Peinelt C, Beck A, Parvez S, Monteilh-Zoller M et al. 2007. CRACM1, CRACM2, and CRACM3 are store-operated Ca²⁺ channels with distinct functional properties. Curr. Biol. 17:794–800
    [Google Scholar]
31. 31. 

    Mercer JC, Dehaven WI, Smyth JT, Wedel B, Boyles RR et al. 2006. Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1. J. Biol. Chem. 281:24979–90
    [Google Scholar]
32. 32. 

    Ay AS, Benzerdjeb N, Sevestre H, Ahidouch A, Ouadid-Ahidouch H. 2013. Orai3 constitutes a native store-operated calcium entry that regulates non small cell lung adenocarcinoma cell proliferation. PLOS ONE 8:e72889
    [Google Scholar]
33. 33. 

    Motiani RK, Abdullaev IF, Trebak M 2010. A novel native store-operated calcium channel encoded by Orai3: selective requirement of Orai3 versus Orai1 in estrogen receptor-positive versus estrogen receptor-negative breast cancer cells. J. Biol. Chem. 285:19173–83
    [Google Scholar]
34. 34. 

    Tsvilovskyy V, Solís-López A, Schumacher D, Medert R, Roers A et al. 2018. Deletion of Orai2 augments endogenous CRAC currents and degranulation in mast cells leading to enhanced anaphylaxis. Cell Calcium 71:24–33
    [Google Scholar]
35. 35. 

    Vaeth M, Yang J, Yamashita M, Zee I, Eckstein M et al. 2017. ORAI2 modulates store-operated calcium entry and T cell-mediated immunity. Nat. Commun. 8:14714
    [Google Scholar]
36. 36. 

    Yoast RE, Emrich SM, Zhang X, Xin P, Johnson MT et al. 2020. The native ORAI channel trio underlies the diversity of Ca²⁺ signaling events. Nat. Commun. 11:2444
    [Google Scholar]
37. 37. 

    Eckstein M, Vaeth M, Aulestia FJ, Costiniti V, Kassam SN et al. 2019. Differential regulation of Ca²⁺ influx by ORAI channels mediates enamel mineralization. Sci. Signal. 12:eaav4663
    [Google Scholar]
38. 38. 

    Zhang X, Gonzalez-Cobos JC, Schindl R, Muik M, Ruhle B et al. 2013. Mechanisms of STIM1 activation of store-independent leukotriene C4-regulated Ca²⁺ channels. Mol. Cell. Biol. 33:3715–23
    [Google Scholar]
39. 39. 

    Ben-Kasus Nissim T, Zhang X, Elazar A, Roy S, Stolwijk JA et al. 2017. Mitochondria control store-operated Ca²⁺ entry through Na⁺ and redox signals. EMBO J 36:797–815
    [Google Scholar]
40. 40. 

    Bogeski I, Kummerow C, Al-Ansary D, Schwarz EC, Koehler R et al. 2010. Differential redox regulation of ORAI ion channels: a mechanism to tune cellular calcium signaling. Sci. Signal. 3:ra24
    [Google Scholar]
41. 41. 

    Faouzi M, Hague F, Potier M, Ahidouch A, Sevestre H, Ouadid-Ahidouch H. 2011. Down-regulation of Orai3 arrests cell-cycle progression and induces apoptosis in breast cancer cells but not in normal breast epithelial cells. J. Cell. Physiol. 226:542–51
    [Google Scholar]
42. 42. 

    Faouzi M, Kischel P, Hague F, Ahidouch A, Benzerdjeb N et al. 2013. ORAI3 silencing alters cell proliferation and cell cycle progression via c-myc pathway in breast cancer cells. Biochim. Biophys. Acta Mol. Cell Res. 1833:752–60
    [Google Scholar]
43. 43. 

    Motiani RK, Hyzinski-García MC, Zhang X, Henkel MM, Abdullaev IF et al. 2013. STIM1 and Orai1 mediate CRAC channel activity and are essential for human glioblastoma invasion. Pflügers Arch. . Eur. J. Physiol. 465:1249–60
    [Google Scholar]
44. 44. 

    Brandman O, Liou J, Park WS, Meyer T 2007. STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca²⁺ levels. Cell 131:1327–39
    [Google Scholar]
45. 45. 

    Emrich SM, Yoast RE, Xin P, Arige V, Wagner LE et al. 2021. Omnitemporal choreographies of all five STIM/Orai and IP₃Rs underlie the complexity of mammalian Ca²⁺ signaling. Cell Rep 34:108760
    [Google Scholar]
46. 46. 

    Subedi KP, Ong HL, Son GY, Liu X, Ambudkar IS. 2018. STIM2 induces activated conformation of STIM1 to control Orai1 function in ER-PM junctions. Cell Rep 23:522–34
    [Google Scholar]
47. 47. 

    Ong HL, de Souza LB, Zheng C, Cheng KT, Liu X et al. 2015. STIM2 enhances receptor-stimulated Ca²⁺ signaling by promoting recruitment of STIM1 to the endoplasmic reticulum-plasma membrane junctions. Sci. Signal. 8:ra3
    [Google Scholar]
48. 48. 

    Berna-Erro A, Braun A, Kraft R, Kleinschnitz C, Schuhmann MK et al. 2009. STIM2 regulates capacitive Ca²⁺ entry in neurons and plays a key role in hypoxic neuronal cell death. Sci. Signal. 2:ra67
    [Google Scholar]
49. 49. 

    Emrich SM, Yoast RE, Xin P, Zhang X, Pathak T et al. 2019. Cross-talk between N-terminal and C-terminal domains in stromal interaction molecule 2 (STIM2) determines enhanced STIM2 sensitivity. J. Biol. Chem. 294:6318–32
    [Google Scholar]
50. 50. 

    Nelson HA, Leech CA, Kopp RF, Roe MW. 2018. Interplay between ER Ca²⁺ binding proteins, STIM1 and STIM2, is required for store-operated Ca²⁺ entry. Int. J. Mol. Sci. 19:1522
    [Google Scholar]
51. 51. 

    Miederer AM, Alansary D, Schwar G, Lee PH, Jung M et al. 2015. A STIM2 splice variant negatively regulates store-operated calcium entry. Nat. Commun. 6:6899
    [Google Scholar]
52. 52. 

    Rana A, Yen M, Sadaghiani AM, Malmersjo S, Park CY et al. 2015. Alternative splicing converts STIM2 from an activator to an inhibitor of store-operated calcium channels. J. Cell Biol. 209:653–69
    [Google Scholar]
53. 53. 

    Kim KM, Rana A, Park CY 2019. Orai1 inhibitor STIM2β regulates myogenesis by controlling SOCE dependent transcriptional factors. Sci. Rep. 9:10794
    [Google Scholar]
54. 54. 

    Zhou Y, Nwokonko RM, Cai X, Loktionova NA, Abdulqadir R et al. 2018. Cross-linking of Orai1 channels by STIM proteins. PNAS 115:E3398–407
    [Google Scholar]
55. 55. 

    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. 194:335–46
    [Google Scholar]
56. 56. 

    Ramesh G, Jarzembowski L, Schwarz Y, Poth V, Konrad M et al. 2021. A short isoform of STIM1 confers frequency-dependent synaptic enhancement. Cell Rep 34:108844
    [Google Scholar]
57. 57. 

    Vaeth M, Kahlfuss S, Feske S 2020. CRAC channels and calcium signaling in T cell-mediated immunity. Trends Immunol 41:878–901
    [Google Scholar]
58. 58. 

    Feske S, Wulff H, Skolnik EY. 2015. Ion channels in innate and adaptive immunity. Annu. Rev. Immunol. 33:291–353
    [Google Scholar]
59. 59. 

    Gwack Y, Srikanth S, Oh-Hora M, Hogan PG, Lamperti ED et al. 2008. Hair loss and defective T- and B-cell function in mice lacking ORAI1. Mol. Cell. Biol. 28:5209–22
    [Google Scholar]
60. 60. 

    McCarl CA, Khalil S, Ma J, Oh-hora M, Yamashita M et al. 2010. Store-operated Ca²⁺ entry through ORAI1 is critical for T cell-mediated autoimmunity and allograft rejection. J. Immunol. 185:5845–58
    [Google Scholar]
61. 61. 

    Inayama M, Suzuki Y, Yamada S, Kurita T, Yamamura H et al. 2015. Orai1–Orai2 complex is involved in store-operated calcium entry in chondrocyte cell lines. Cell Calcium 57:337–47
    [Google Scholar]
62. 62. 

    Scremin E, Agostini M, Leparulo A, Pozzan T, Greotti E, Fasolato C 2020. ORAI2 down-regulation potentiates SOCE and decreases Aβ42 accumulation in human neuroglioma cells. Int. J. Mol. Sci. 21:5288
    [Google Scholar]
63. 63. 

    Desai PN, Zhang X, Wu S, Janoshazi A, Bolimuntha S et al. 2015. Multiple types of calcium channels arising from alternative translation initiation of the Orai1 message. Sci. Signal. 8:ra74
    [Google Scholar]
64. 64. 

    Thompson JL, Mignen O, Shuttleworth TJ. 2013. The ARC channel—an endogenous store-independent Orai channel. Curr. Top Membr. 71:125–48
    [Google Scholar]
65. 65. 

    Zhang X, Zhang W, Gonzalez-Cobos JC, Jardin I, Romanin C et al. 2014. Complex role of STIM1 in the activation of store-independent Orai1/3 channels. J. Gen. Physiol. 143:345–59
    [Google Scholar]
66. 66. 

    Ye Z, Shen Y, Jin K, Qiu J, Hu B et al. 2021. Arachidonic acid-regulated calcium signaling in T cells from patients with rheumatoid arthritis promotes synovial inflammation. Nat. Commun. 12:907
    [Google Scholar]
67. 67. 

    Fuchs S, Rensing-Ehl A, Speckmann C, Bengsch B, Schmitt-Graeff A et al. 2012. Antiviral and regulatory T cell immunity in a patient with stromal interaction molecule 1 deficiency. J. Immunol. 188:1523–33
    [Google Scholar]
68. 68. 

    Schaballie H, Rodriguez R, Martin E, Moens L, Frans G et al. 2015. A novel hypomorphic mutation in STIM1 results in a late-onset immunodeficiency. J. Allergy Clin. Immunol. 136:816–19.e4
    [Google Scholar]
69. 69. 

    Pearce EL, Poffenberger MC, Chang CH, Jones RG. 2013. Fueling immunity: insights into metabolism and lymphocyte function. Science 342:1242454
    [Google Scholar]
70. 70. 

    Vaeth M, Maus M, Klein-Hessling S, Freinkman E, Yang J et al. 2017. Store-operated Ca²⁺ entry controls clonal expansion of T cells through metabolic reprogramming. Immunity 47:664–79.e6
    [Google Scholar]
71. 71. 

    Azzi JR, Sayegh MH, Mallat SG. 2013. Calcineurin inhibitors: 40 years later, can't live without.…. J. Immunol. 191:5785–91
    [Google Scholar]
72. 72. 

    Golubovskaya V, Wu L. 2016. Different subsets of T cells, memory, effector functions, and CAR-T immunotherapy. Cancers 8:36
    [Google Scholar]
73. 73. 

    Wing JB, Lim EL, Sakaguchi S. 2020. Control of foreign Ag-specific Ab responses by Treg and Tfr. Immunol. Rev. 296:104–19
    [Google Scholar]
74. 74. 

    Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S et al. 2011. Foxp³⁺ follicular regulatory T cells control the germinal center response. Nat. Med. 17:975–82
    [Google Scholar]
75. 75. 

    Vaeth M, Eckstein M, Shaw PJ, Kozhaya L, Yang J et al. 2016. Store-operated Ca²⁺ entry in follicular T cells controls humoral immune responses and autoimmunity. Immunity 44:1350–64
    [Google Scholar]
76. 76. 

    Oh-Hora M, Yamashita M, Hogan PG, Sharma S, Lamperti E et al. 2008. Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nat. Immunol. 9:432–43
    [Google Scholar]
77. 77. 

    Greimers R, Trebak M, Moutschen M, Jacobs N, Boniver J. 1996. Improved four-color flow cytometry method using fluo-3 and triple immunofluorescence for analysis of intracellular calcium ion ([Ca²⁺]_i) fluxes among mouse lymph node B- and T-lymphocyte subsets. Cytometry 23:205–17
    [Google Scholar]
78. 78. 

    Kircher S, Merino-Wong M, Niemeyer BA, Alansary D. 2018. Profiling calcium signals of in vitro polarized human effector CD4⁺ T cells. Biochim. Biophys. Acta Mol. Cell Res. 1865:932–43
    [Google Scholar]
79. 79. 

    Vaeth M, Wang YH, Eckstein M, Yang J, Silverman GJ et al. 2019. Tissue resident and follicular Treg cell differentiation is regulated by CRAC channels. Nat. Commun. 10:1183
    [Google Scholar]
80. 80. 

    Oh-Hora M, Lu X, Shiokawa M, Takayanagi H, Yamasaki S. 2019. Stromal interaction molecule deficiency in T cells promotes spontaneous follicular helper T cell development and causes type 2 immune disorders. J. Immunol. 202:2616–27
    [Google Scholar]
81. 81. 

    Tesmer LA, Lundy SK, Sarkar S, Fox DA 2008. Th17 cells in human disease. Immunol. Rev. 223:87–113
    [Google Scholar]
82. 82. 

    Kim KD, Srikanth S, Tan YV, Yee MK, Jew M et al. 2014. Calcium signaling via Orai1 is essential for induction of the nuclear orphan receptor pathway to drive Th17 differentiation. J. Immunol. 192:110–22
    [Google Scholar]
83. 83. 

    Ma J, McCarl CA, Khalil S, Lüthy K, Feske S 2010. T-cell-specific deletion of STIM1 and STIM2 protects mice from EAE by impairing the effector functions of Th1 and Th17 cells. Eur. J. Immunol. 40:3028–42
    [Google Scholar]
84. 84. 

    Kaufmann U, Kahlfuss S, Yang J, Ivanova E, Koralov SB, Feske S. 2019. Calcium signaling controls pathogenic Th17 cell-mediated inflammation by regulating mitochondrial function. Cell Metab. 29:1104–18.e6
    [Google Scholar]
85. 85. 

    Matsumoto M, Fujii Y, Baba A, Hikida M, Kurosaki T, Baba Y. 2011. The calcium sensors STIM1 and STIM2 control B cell regulatory function through interleukin-10 production. Immunity 34:703–14
    [Google Scholar]
86. 86. 

    Tang H, Wang H, Lin Q, Fan F, Zhang F et al. 2017. Loss of IP₃ receptor-mediated Ca²⁺ release in mouse B cells results in abnormal B cell development and function. J. Immunol. 199:570–80
    [Google Scholar]
87. 87. 

    Akkaya M, Pierce SK. 2019. From zero to sixty and back to zero again: the metabolic life of B cells. Curr. Opin. Immunol. 57:1–7
    [Google Scholar]
88. 88. 

    Berry CT, Liu X, Myles A, Nandi S, Chen YH et al. 2020. BCR-induced Ca²⁺ signals dynamically tune survival, metabolic reprogramming, and proliferation of naive B cells. Cell Rep 31:107474
    [Google Scholar]
89. 89. 

    Akkaya M, Traba J, Roesler AS, Miozzo P, Akkaya B et al. 2018. Second signals rescue B cells from activation-induced mitochondrial dysfunction and death. Nat. Immunol. 19:871–84
    [Google Scholar]
90. 90. 

    Luo W, Weisel F, Shlomchik MJ. 2018. B cell receptor and CD40 signaling are rewired for synergistic induction of the c-Myc transcription factor in germinal center B cells. Immunity 48:313–26.e5
    [Google Scholar]
91. 91. 

    Weisel FJ, Mullett SJ, Elsner RA, Menk AV, Trivedi N et al. 2020. Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis. Nat. Immunol. 21:331–42
    [Google Scholar]
92. 92. 

    Maus M, Cuk M, Patel B, Lian J, Ouimet M et al. 2017. Store-operated Ca²⁺ entry controls induction of lipolysis and the transcriptional reprogramming to lipid metabolism. Cell Metab 25:698–712
    [Google Scholar]
93. 93. 

    Demaurex N, Saul S. 2018. The role of STIM proteins in neutrophil functions. J. Physiol. 596:2699–708
    [Google Scholar]
94. 94. 

    Vig M, DeHaven WI, Bird GS, Billingsley JM, Wang H et al. 2008. Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store-operated calcium release-activated calcium channels. Nat. Immunol. 9:89–96
    [Google Scholar]
95. 95. 

    Grimes D, Johnson R, Pashos M, Cummings C, Kang C et al. 2020. ORAI1 and ORAI2 modulate murine neutrophil calcium signaling, cellular activation, and host defense. PNAS 117:24403–14
    [Google Scholar]
96. 96. 

    Vaeth M, Zee I, Concepcion AR, Maus M, Shaw P et al. 2015. Ca²⁺ signaling but not store-operated Ca²⁺ entry is required for the function of macrophages and dendritic cells. J. Immunol. 195:1202–17
    [Google Scholar]
97. 97. 

    Freund-Brown J, Choa R, Singh BK, Robertson TF, Ferry GM et al. 2017. Cutting edge: murine NK cells degranulate and retain cytotoxic function without store-operated calcium entry. J. Immunol. 199:1973–78
    [Google Scholar]
98. 98. 

    Srikanth S, Woo JS, Wu B, El-Sherbiny YM, Leung J et al. 2019. The Ca²⁺ sensor STIM1 regulates the type I interferon response by retaining the signaling adaptor STING at the endoplasmic reticulum. Nat. Immunol. 20:152–62
    [Google Scholar]
99. 99. 

    Nunes-Hasler P, Maschalidi S, Lippens C, Castelbou C, Bouvet S et al. 2017. STIM1 promotes migration, phagosomal maturation and antigen cross-presentation in dendritic cells. Nat. Commun. 8:1852
    [Google Scholar]
100. 100. 

     Shinde AV, Motiani RK, Zhang X, Abdullaev IF, Adam AP et al. 2013. STIM1 controls endothelial barrier function independently of Orai1 and Ca²⁺ entry. Sci. Signal. 6:ra18
     [Google Scholar]
101. 101. 

     Chauhan AS, Liu X, Jing J, Lee H, Yadav RK et al. 2019. STIM2 interacts with AMPK and regulates calcium-induced AMPK activation. FASEB J. 33:2957–70
     [Google Scholar]
102. 102. 

     Thillaiappan NB, Chavda AP, Tovey SC, Prole DL, Taylor CW. 2017. Ca²⁺ signals initiate at immobile IP₃ receptors adjacent to ER-plasma membrane junctions. Nat. Commun. 8:1505
     [Google Scholar]
103. 103. 

     Sampieri A, Santoyo K, Asanov A, Vaca L 2018. Association of the IP₃R to STIM1 provides a reduced intraluminal calcium microenvironment, resulting in enhanced store-operated calcium entry. Sci. Rep. 8:13252
     [Google Scholar]
104. 104. 

     Lang F, Münzer P, Gawaz M, Borst O. 2013. Regulation of STIM1/Orai1-dependent Ca²⁺ signalling in platelets. Thrombos. Haemostas. 110:925–30
     [Google Scholar]
105. 105. 

     Gilio K, van Kruchten R, Braun A, Berna-Erro A, Feijge MA et al. 2010. Roles of platelet STIM1 and Orai1 in glycoprotein VI- and thrombin-dependent procoagulant activity and thrombus formation. J. Biol. Chem. 285:23629–38
     [Google Scholar]
106. 106. 

     Braun A, Varga-Szabo D, Kleinschnitz C, Pleines I, Bender M et al. 2009. Orai1 (CRACM1) is the platelet SOC channel and essential for pathological thrombus formation. Blood 113:2056–63
     [Google Scholar]
107. 107. 

     Varga-Szabo D, Braun A, Kleinschnitz C, Bender M, Pleines I et al. 2008. The calcium sensor STIM1 is an essential mediator of arterial thrombosis and ischemic brain infarction. J. Exp. Med. 205:1583–91
     [Google Scholar]
108. 108. 

     Markello T, Chen D, Kwan JY, Horkayne-Szakaly I, Morrison A et al. 2015. York platelet syndrome is a CRAC channelopathy due to gain-of-function mutations in STIM1. Mol. Genet. Metab. 114:474–82
     [Google Scholar]
109. 109. 

     Morin G, Bruechle NO, Singh AR, Knopp C, Jedraszak G et al. 2014. Gain-of-function mutation in STIM1 (P.R304W) is associated with Stormorken syndrome. Hum. Mutat. 35:1221–32
     [Google Scholar]
110. 110. 

     Misceo D, Holmgren A, Louch WE, Holme PA, Mizobuchi M et al. 2014. A dominant STIM1 mutation causes Stormorken syndrome. Hum. Mutat. 35:556–64
     [Google Scholar]
111. 111. 

     Nesin V, Wiley G, Kousi M, Ong EC, Lehmann T et al. 2014. Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis. PNAS 111:4197–202
     [Google Scholar]
112. 112. 

     Fahrner M, Stadlbauer M, Muik M, Rathner P, Stathopulos P et al. 2018. A dual mechanism promotes switching of the Stormorken STIM1 R304W mutant into the activated state. Nat. Commun. 9:825
     [Google Scholar]
113. 113. 

     Böhm J, Chevessier F, Maues De Paula A, Koch C, Attarian S et al. 2013. Constitutive activation of the calcium sensor STIM1 causes tubular-aggregate myopathy. Am. J. Hum. Genet. 92:271–78
     [Google Scholar]
114. 114. 

     Grosse J, Braun A, Varga-Szabo D, Beyersdorf N, Schneider B et al. 2007. An EF hand mutation in Stim1 causes premature platelet activation and bleeding in mice. J. Clin. Investig. 117:3540–50
     [Google Scholar]
115. 115. 

     Cordero-Sanchez C, Riva B, Reano S, Clemente N, Zaggia I et al. 2019. A luminal EF-hand mutation in STIM1 in mice causes the clinical hallmarks of tubular aggregate myopathy. Dis. Models Mech. 13:dmm041111
     [Google Scholar]
116. 116. 

     Gamage TH, Gunnes G, Lee RH, Louch WE, Holmgren A et al. 2018. STIM1 R304W causes muscle degeneration and impaired platelet activation in mice. Cell Calcium 76:87–100
     [Google Scholar]
117. 117. 

     Silva-Rojas R, Treves S, Jacobs H, Kessler P, Messaddeq N et al. 2019. STIM1 over-activation generates a multi-systemic phenotype affecting the skeletal muscle, spleen, eye, skin, bones and immune system in mice. Hum. Mol. Genet. 28:1579–93
     [Google Scholar]
118. 118. 

     Eckstein M, Aulestia FJ, Nurbaeva MK, Lacruz RS. 2018. Altered Ca²⁺ signaling in enamelopathies. Biochim. Biophys. Acta Mol. Cell Res. 1865:1778–85
     [Google Scholar]
119. 119. 

     Paine ML, Snead ML. 2005. Tooth developmental biology: disruptions to enamel-matrix assembly and its impact on biomineralization. Orthodont. Craniofac. Res. 8:239–51
     [Google Scholar]
120. 120. 

     Baranova J, Büchner D, Götz W, Schulze M, Tobiasch E. 2020. Tooth formation: Are the hardest tissues of human body hard to regenerate?. Int. J. Mol. Sci. 21:4031
     [Google Scholar]
121. 121. 

     Lacruz RS, Smith CE, Bringas P Jr., Chen YB, Smith SM et al. 2012. Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling. J. Cell. Physiol. 227:2264–75
     [Google Scholar]
122. 122. 

     Nurbaeva MK, Eckstein M, Concepcion AR, Smith CE, Srikanth S et al. 2015. Dental enamel cells express functional SOCE channels. Sci. Rep. 5:15803
     [Google Scholar]
123. 123. 

     Eckstein M, Vaeth M, Fornai C, Vinu M, Bromage TG et al. 2017. Store-operated Ca²⁺ entry controls ameloblast cell function and enamel development. JCI Insight 2:e91166
     [Google Scholar]
124. 124. 

     Furukawa Y, Haruyama N, Nikaido M, Nakanishi M, Ryu N et al. 2017. Stim1 regulates enamel mineralization and ameloblast modulation. J. Dent. Res. 96:1422–29
     [Google Scholar]
125. 125. 

     Berg J, Yang H, Jan LY 2012. Ca²⁺-activated Cl⁻ channels at a glance. J. Cell Sci. 125:1367–71
     [Google Scholar]
126. 126. 

     Concepcion AR, Vaeth M, Wagner LE2nd, Eckstein M, Hecht L et al. 2016. Store-operated Ca²⁺ entry regulates Ca²⁺-activated chloride channels and eccrine sweat gland function. J. Clin. Investig. 126:4303–18
     [Google Scholar]
127. 127. 

     Xing J, Petranka JG, Davis FM, Desai PN, Putney JW, Bird GS. 2014. Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling and function. J. Physiol. 592:927–39
     [Google Scholar]
128. 128. 

     Davis FM, Janoshazi A, Janardhan KS, Steinckwich N, D'Agostin DM et al. 2015. Essential role of Orai1 store-operated calcium channels in lactation. PNAS 112:5827–32
     [Google Scholar]
129. 129. 

     Davis FM, Goulding EH, D'Agostin DM, Janardhan KS, Cummings CA et al. 2016. Male infertility in mice lacking the store-operated Ca²⁺ channel Orai1. Cell Calcium 59:189–97
     [Google Scholar]
130. 130. 

     Mosinger B, Redding KM, Parker MR, Yevshayeva V, Yee KK et al. 2013. Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility. PNAS 110:12319–24
     [Google Scholar]
131. 131. 

     Ahuja M, Schwartz DM, Tandon M, Son A, Zeng M et al. 2017. Orai1-mediated antimicrobial secretion from pancreatic acini shapes the gut microbiome and regulates gut innate immunity. Cell Metab 25:635–46
     [Google Scholar]
132. 132. 

     Michelucci A, Garcia-Castaneda M, Boncompagni S, Dirksen RT 2018. Role of STIM1/ORAI1-mediated store-operated Ca²⁺ entry in skeletal muscle physiology and disease. Cell Calcium 76:101–15
     [Google Scholar]
133. 133. 

     Trebak M, Zhang W, Ruhle B, Henkel MM, Gonzalez-Cobos JC et al. 2013. What role for store-operated Ca²⁺ entry in muscle?. Microcirculation 20:330–36
     [Google Scholar]
134. 134. 

     Feske S. 2010. CRAC channelopathies. Pflügers Arch. . Eur. J. Physiol. 460:417–35
     [Google Scholar]
135. 135. 

     Potier M, Gonzalez JC, Motiani RK, Abdullaev IF, Bisaillon JM et al. 2009. Evidence for STIM1- and Orai1-dependent store-operated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration. FASEB J 23:2425–37
     [Google Scholar]
136. 136. 

     Trebak M. 2012. STIM/Orai signalling complexes in vascular smooth muscle. J. Physiol. 590:4201–8
     [Google Scholar]
137. 137. 

     Zhang W, Halligan KE, Zhang X, Bisaillon JM, Gonzalez-Cobos JC et al. 2011. Orai1-mediated I (CRAC) is essential for neointima formation after vascular injury. Circ. Res. 109:534–42
     [Google Scholar]
138. 138. 

     Zhao G, Li T, Brochet DX, Rosenberg PB, Lederer WJ. 2015. STIM1 enhances SR Ca²⁺ content through binding phospholamban in rat ventricular myocytes. PNAS 112:E4792–801
     [Google Scholar]
139. 139. 

     Cacheux M, Strauss B, Raad N, Ilkan Z, Hu J et al. 2019. Cardiomyocyte-specific STIM1 (stromal interaction molecule 1) depletion in the adult heart promotes the development of arrhythmogenic discordant alternans. Circ. Arrhythm. Electrophysiol. 12:e007382
     [Google Scholar]
140. 140. 

     Collins HE, He L, Zou L, Qu J, Zhou L et al. 2014. Stromal interaction molecule 1 is essential for normal cardiac homeostasis through modulation of ER and mitochondrial function. Am. J. Physiol. Heart Circ. Physiol. 306:H1231–39
     [Google Scholar]
141. 141. 

     Benard L, Oh JG, Cacheux M, Lee A, Nonnenmacher M et al. 2016. Cardiac Stim1 silencing impairs adaptive hypertrophy and promotes heart failure through inactivation of mTORC2/Akt signaling. Circulation 133:1458–71
     [Google Scholar]
142. 142. 

     Mancarella S, Potireddy S, Wang Y, Gao H, Gandhirajan RK et al. 2013. Targeted STIM deletion impairs calcium homeostasis, NFAT activation, and growth of smooth muscle. FASEB J. 27:893–906
     [Google Scholar]
143. 143. 

     Kassan M, Ait-Aissa K, Radwan E, Mali V, Haddox S et al. 2016. Essential role of smooth muscle STIM1 in hypertension and cardiovascular dysfunction. Arterioscler. Thromb. Vasc. Biol. 36:1900–9
     [Google Scholar]
144. 144. 

     Kassan M, Zhang W, Aissa KA, Stolwijk J, Trebak M, Matrougui K 2015. Differential role for stromal interacting molecule 1 in the regulation of vascular function. Pflügers Arch. . Eur. J. Physiol. 467:1195–202
     [Google Scholar]
145. 145. 

     Zheng H, Drumm BT, Earley S, Sung TS, Koh SD, Sanders KM. 2018. SOCE mediated by STIM and Orai is essential for pacemaker activity in the interstitial cells of Cajal in the gastrointestinal tract. Sci. Signal. 11:eaaq0918
     [Google Scholar]
146. 146. 

     Johnson M, Trebak M 2019. ORAI channels in cellular remodeling of cardiorespiratory disease. Cell Calcium 79:1–10
     [Google Scholar]
147. 147. 

     Bartoli F, Bailey MA, Rode B, Mateo P, Antigny F et al. 2020. Orai1 channel inhibition preserves left ventricular systolic function and normal Ca²⁺ handling after pressure overload. Circulation 141:199–216
     [Google Scholar]
148. 148. 

     Hulot JS, Fauconnier J, Ramanujam D, Chaanine A, Aubart F et al. 2011. Critical role for stromal interaction molecule 1 in cardiac hypertrophy. Circulation 124:796–805
     [Google Scholar]
149. 149. 

     Correll RN, Goonasekera SA, van Berlo JH, Burr AR, Accornero F et al. 2015. STIM1 elevation in the heart results in aberrant Ca²⁺ handling and cardiomyopathy. J. Mol. Cell. Cardiol. 87:38–47
     [Google Scholar]
150. 150. 

     Johnson MT, Gudlur A, Zhang X, Xin P, Emrich SM et al. 2020. L-type Ca²⁺ channel blockers promote vascular remodeling through activation of STIM proteins. PNAS 117:17369–80
     [Google Scholar]
151. 151. 

     Spinelli AM, Gonzalez-Cobos JC, Zhang X, Motiani RK, Rowan S et al. 2012. Airway smooth muscle STIM1 and Orai1 are upregulated in asthmatic mice and mediate PDGF-activated SOCE, CRAC currents, proliferation, and migration. Pflügers Arch. . Eur. J. Physiol. 464:481–92
     [Google Scholar]
152. 152. 

     Collins SR, Meyer T. 2011. Evolutionary origins of STIM1 and STIM2 within ancient Ca²⁺ signaling systems. Trends Cell Biol. 21:202–11
     [Google Scholar]
153. 153. 

     Gammons J, Trebak M, Mancarella S. 2021. Cardiac-specific deletion of Orai3 leads to severe dilated cardiomyopathy and heart failure in mice. J. Am. Heart Assoc. 10:e019486
     [Google Scholar]
154. 154. 

     Saliba Y, Keck M, Marchand A, Atassi F, Ouille A et al. 2015. Emergence of Orai3 activity during cardiac hypertrophy. Cardiovasc. Res. 105:248–59
     [Google Scholar]
155. 155. 

     Gonzalez-Cobos JC, Zhang X, Zhang W, Ruhle B, Motiani RK et al. 2013. Store-independent Orai1/3 channels activated by intracrine leukotriene C4: role in neointimal hyperplasia. Circ. Res. 112:1013–25
     [Google Scholar]
156. 156. 

     Zhang W, Zhang X, Gonzalez-Cobos JC, Stolwijk JA, Matrougui K, Trebak M 2015. Leukotriene-C4 synthase, a critical enzyme in the activation of store-independent Orai1/Orai3 channels, is required for neointimal hyperplasia. J. Biol. Chem. 290:5015–27
     [Google Scholar]
157. 157. 

     Moccia F, Zuccolo E, Soda T, Tanzi F, Guerra G et al. 2015. Stim and Orai proteins in neuronal Ca²⁺ signaling and excitability. Front. Cell. Neurosci. 9:153
     [Google Scholar]
158. 158. 

     Sun S, Zhang H, Liu J, Popugaeva E, Xu NJ et al. 2014. Reduced synaptic STIM2 expression and impaired store-operated calcium entry cause destabilization of mature spines in mutant presenilin mice. Neuron 82:79–93
     [Google Scholar]
159. 159. 

     Stegner D, Hofmann S, Schuhmann MK, Kraft P, Herrmann AM et al. 2019. Loss of Orai2-mediated capacitative Ca²⁺ entry is neuroprotective in acute ischemic stroke. Stroke 50:3238–45
     [Google Scholar]
160. 160. 

     Hartmann J, Karl RM, Alexander RP, Adelsberger H, Brill MS et al. 2014. STIM1 controls neuronal Ca²⁺ signaling, mGluR1-dependent synaptic transmission, and cerebellar motor behavior. Neuron 82:635–44
     [Google Scholar]
161. 161. 

     Chen-Engerer HJ, Hartmann J, Karl RM, Yang J, Feske S, Konnerth A 2019. Two types of functionally distinct Ca²⁺ stores in hippocampal neurons. Nat. Commun. 10:3223
     [Google Scholar]
162. 162. 

     Maneshi MM, Toth AB, Ishii T, Hori K, Tsujikawa S et al. 2020. Orai1 channels are essential for amplification of glutamate-evoked Ca²⁺ signals in dendritic spines to regulate working and associative memory. Cell Rep. 33:108464
     [Google Scholar]
163. 163. 

     Dou Y, Xia J, Gao R, Gao X, Munoz FM et al. 2018. Orai1 plays a crucial role in central sensitization by modulating neuronal excitability. J. Neurosci. 38:887–900
     [Google Scholar]
164. 164. 

     Maciąg F, Majewski Ł, Boguszewski PM, Gupta RK, Wasilewska I et al. 2019. Behavioral and electrophysiological changes in female mice overexpressing ORAI1 in neurons. Biochim. Biophys. Acta Mol. Cell Res. 1866:1137–50
     [Google Scholar]
165. 165. 

     Garcia-Alvarez G, Shetty MS, Lu B, Yap KA, Oh-Hora M et al. 2015. Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes. Front. Behav. Neurosci. 9:180
     [Google Scholar]
166. 166. 

     Garcia-Alvarez G, Lu B, Yap KA, Wong LC, Thevathasan JV et al. 2015. STIM2 regulates PKA-dependent phosphorylation and trafficking of AMPARs. Mol. Biol. Cell 26:1141–59
     [Google Scholar]
167. 167. 

     Dittmer PJ, Wild AR, Dell'Acqua ML, Sather WA. 2017. STIM1 Ca²⁺ sensor control of L-type Ca²⁺-channel-dependent dendritic spine structural plasticity and nuclear signaling. Cell Rep. 19:321–34
     [Google Scholar]
168. 168. 

     Volterra A, Liaudet N, Savtchouk I. 2014. Astrocyte Ca²⁺ signalling: an unexpected complexity. Nat. Rev. Neurosci. 15:327–35
     [Google Scholar]
169. 169. 

     Kwon J, An H, Sa M, Won J, Shin JI, Lee CJ. 2017. Orai1 and Orai3 in combination with Stim1 mediate the majority of store-operated calcium entry in astrocytes. Exp. Neurobiol. 26:42–54
     [Google Scholar]
170. 170. 

     Gao X, Xia J, Munoz FM, Manners MT, Pan R et al. 2016. STIMs and Orai1 regulate cytokine production in spinal astrocytes. J. Neuroinflamm. 13:126
     [Google Scholar]
171. 171. 

     Michaelis M, Nieswandt B, Stegner D, Eilers J, Kraft R 2015. STIM1, STIM2, and Orai1 regulate store-operated calcium entry and purinergic activation of microglia. Glia 63:652–63
     [Google Scholar]
172. 172. 

     Heo DK, Lim HM, Nam JH, Lee MG, Kim JY 2015. Regulation of phagocytosis and cytokine secretion by store-operated calcium entry in primary isolated murine microglia. Cell. Signal. 27:177–86
     [Google Scholar]
173. 173. 

     Toth AB, Hori K, Novakovic MM, Bernstein NG, Lambot L, Prakriya M 2019. CRAC channels regulate astrocyte Ca²⁺ signaling and gliotransmitter release to modulate hippocampal GABAergic transmission. Sci. Signal. 12:eaaw5450
     [Google Scholar]