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IP3 receptor signaling and endothelial barrier function

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Abstract

The endothelium, a monolayer of endothelial cells lining vessel walls, maintains tissue-fluid homeostasis by restricting the passage of the plasma proteins and blood cells into the interstitium. The ion Ca2+, a ubiquitous secondary messenger, initiates signal transduction events in endothelial cells that is critical to control of vascular tone and endothelial permeability. The ion Ca2+ is stored inside the intracellular organelles and released into the cytosol in response to environmental cues. The inositol 1,4,5-trisphosphate (IP3) messenger facilitates Ca2+ release through IP3 receptors which are Ca2+-selective intracellular channels located within the membrane of the endoplasmic reticulum. Binding of IP3 to the IP3Rs initiates assembly of IP3R clusters, a key event responsible for amplification of Ca2+ signals in endothelial cells. This review discusses emerging concepts related to architecture and dynamics of IP3R clusters, and their specific role in propagation of Ca2+ signals in endothelial cells.

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Modified from Fan et al. [133] with permission of the publisher. Copyright ©2015, Nature Publishing Group

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References

  1. Laubichler MD, Aird WC, Maienschein J (2007) The endothelium in history. In: Endothelial biomedicine. Cambridge University Press, Cambridge, pp 3–20

  2. Busse R, Trogisch G, Bassenge E (1985) The role of endothelium in the control of vascular tone. Basic Res Cardiol 80:475–490

    Article  CAS  PubMed  Google Scholar 

  3. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    Article  CAS  PubMed  Google Scholar 

  4. Pober JS, Sessa WC (2007) Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 7:803–815

    Article  CAS  PubMed  Google Scholar 

  5. Lamalice L, Le Boeuf F, Huot J (2007) Endothelial cell migration during angiogenesis. Circ Res 100:782–794

    Article  CAS  PubMed  Google Scholar 

  6. Komarova Y, Malik AB (2010) Regulation of endothelial permeability via paracellular and transcellular transport pathways. Annu Rev Physiol 72:463–493

    Article  CAS  PubMed  Google Scholar 

  7. Komarova YA, Kruse K, Mehta D, Malik AB (2017) Protein interactions at endothelial junctions and signaling mechanisms regulating endothelial permeability. Circ Res 120:179–206

    Article  CAS  PubMed  Google Scholar 

  8. Bazzoni G, Dejana E (2004) Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 84:869–901

    Article  CAS  PubMed  Google Scholar 

  9. Xie Z, Ghosh CC, Patel R, Iwaki S, Gaskins D, Nelson C, Jones N, Greipp PR, Parikh SM, Druey KM (2012) Vascular endothelial hyperpermeability induces the clinical symptoms of Clarkson disease (the systemic capillary leak syndrome). Blood 119:4321–4332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Avirutnan P, Punyadee N, Noisakran S, Komoltri C, Thiemmeca S, Auethavornanan K, Jairungsri A, Kanlaya R, Tangthawornchaikul N, Puttikhunt C, Pattanakitsakul SN, Yenchitsomanus PT, Mongkolsapaya J, Kasinrerk W et al (2006) Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement. J Infect Dis 193:1078–1088

    Article  CAS  PubMed  Google Scholar 

  11. Wahl-Jensen VM, Afanasieva TA, Seebach J, Stroher U, Feldmann H, Schnittler HJ (2005) Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function. J Virol 79:10442–10450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yang ZY, Duckers HJ, Sullivan NJ, Sanchez A, Nabel EG, Nabel GJ (2000) Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury. Nat Med 6:886–889

    Article  CAS  PubMed  Google Scholar 

  13. Bouillet L, Mannic T, Arboleas M, Subileau M, Massot C, Drouet C, Huber P, Vilgrain I (2011) Hereditary angioedema: key role for kallikrein and bradykinin in vascular endothelial-cadherin cleavage and edema formation. J Allergy Clin Immunol 128:232–234

    Article  PubMed  Google Scholar 

  14. Kaplan AP (2002) Clinical practice. Chronic urticaria and angioedema. N Engl J Med 346:175–179

    Article  PubMed  Google Scholar 

  15. Herwig MC, Tsokos M, Hermanns MI, Kirkpatrick CJ, Muller AM (2013) Vascular endothelial cadherin expression in lung specimens of patients with sepsis-induced acute respiratory distress syndrome and endothelial cell cultures. Pathobiology 80:245–251

    Article  CAS  PubMed  Google Scholar 

  16. Lee WL, Slutsky AS (2010) Sepsis and endothelial permeability. N Engl J Med 363:689–691

    Article  CAS  PubMed  Google Scholar 

  17. Klaassen I, Van Noorden CJ, Schlingemann RO (2013) Molecular basis of the inner blood–retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog Retin Eye Res 34:19–48

    Article  CAS  PubMed  Google Scholar 

  18. Morganti-Kossmann MC, Rancan M, Stahel PF, Kossmann T (2002) Inflammatory response in acute traumatic brain injury: a double-edged sword. Curr Opin Crit Care 8:101–105

    Article  PubMed  Google Scholar 

  19. Zlokovic BV (2006) Remodeling after stroke. Nat Med 12:390–391

    Article  CAS  PubMed  Google Scholar 

  20. Baluna R, Vitetta ES (1997) Vascular leak syndrome: a side effect of immunotherapy. Immunopharmacology 37:117–132

    Article  CAS  PubMed  Google Scholar 

  21. Zhao Y, Vanhoutte PM, Leung SW (2015) Vascular nitric oxide: beyond eNOS. J Pharmacol Sci 129:83–94

    Article  CAS  PubMed  Google Scholar 

  22. Sandoo A, van Zanten JJ, Metsios GS, Carroll D, Kitas GD (2010) The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J 4:302–312

    Article  PubMed  PubMed Central  Google Scholar 

  23. Tousoulis D, Kampoli AM, Tentolouris C, Papageorgiou N, Stefanadis C (2012) The role of nitric oxide on endothelial function. Curr Vasc Pharmacol 10:4–18

    Article  CAS  PubMed  Google Scholar 

  24. Munaron L (2006) Intracellular calcium, endothelial cells and angiogenesis. Recent Pat Anticancer Drug Discov 1:105–119

    Article  CAS  PubMed  Google Scholar 

  25. Cui C, Merritt R, Fu L, Pan Z (2017) Targeting calcium signaling in cancer therapy. Acta Pharm Sin B 7:3–17

    Article  PubMed  Google Scholar 

  26. Kovacic JC, Boehm M (2009) Resident vascular progenitor cells: an emerging role for non-terminally differentiated vessel-resident cells in vascular biology. Stem Cell Res 2:2–15

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pappenheimer JR, Renkin EM, Borrero LM (1951) Filtration, diffusion and molecular sieving through peripheral capillary membranes; a contribution to the pore theory of capillary permeability. Am J Physiol 167:13–46

    CAS  PubMed  Google Scholar 

  28. Del Vecchio PJ, Siflinger-Birnboim A, Shepard JM, Bizios R, Cooper JA, Malik AB (1987) Endothelial monolayer permeability to macromolecules. Fed Proc 46:2511–2515

    PubMed  Google Scholar 

  29. Siflinger-Birnboim A, Del Vecchio PJ, Cooper JA, Blumenstock FA, Shepard JM, Malik AB (1987) Molecular sieving characteristics of the cultured endothelial monolayer. J Cell Physiol 132:111–117

    Article  CAS  PubMed  Google Scholar 

  30. Wright AK, Thompson MR (1975) Hydrodynamic structure of bovine serum albumin determined by transient electric birefringence. Biophys J 15:137–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Peters T Jr (1985) Serum albumin. Adv Protein Chem 37:161–245

    Article  CAS  PubMed  Google Scholar 

  32. Huxley VH, Curry FE (1985) Albumin modulation of capillary permeability: test of an adsorption mechanism. Am J Physiol 248:H264–H273

    CAS  PubMed  Google Scholar 

  33. Huxley VH, Curry FE (1987) Effect of superfusate albumin on single capillary hydraulic conductivity. Am J Physiol 252:H395–H401

    CAS  PubMed  Google Scholar 

  34. Weisberg HF (1978) Osmotic pressure of the serum proteins. Ann Clin Lab Sci 8:155–164

    CAS  PubMed  Google Scholar 

  35. Landis EM, Hortenstine JC (1950) Functional significance of venous blood pressure. Physiol Rev 30:1–32

    CAS  PubMed  Google Scholar 

  36. Reese TS, Karnovsky MJ (1967) Fine structural localization of a blood–brain barrier to exogenous peroxidase. J Cell Biol 34:207–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Simionescu M, Simionescu N, Palade GE (1975) Segmental differentiations of cell junctions in the vascular endothelium. The microvasculature. J Cell Biol 67:863–885

    Article  CAS  PubMed  Google Scholar 

  38. Huttner I, Boutet M, More RH (1973) Gap junctions in arterial endothelium. J Cell Biol 57:247–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Firth JA, Bauman KF, Sibley CP (1983) The intercellular junctions of guinea-pig placental capillaries: a possible structural basis for endothelial solute permeability. J Ultrastruct Res 85:45–57

    Article  CAS  PubMed  Google Scholar 

  40. Leach L, Clark P, Lampugnani MG, Arroyo AG, Dejana E, Firth JA (1993) Immunoelectron characterisation of the inter-endothelial junctions of human term placenta. J Cell Sci 104(Pt 4):1073–1081

    CAS  PubMed  Google Scholar 

  41. Tamura K, Shan WS, Hendrickson WA, Colman DR, Shapiro L (1998) Structure–function analysis of cell adhesion by neural (N-) cadherin. Neuron 20:1153–1163

    Article  CAS  PubMed  Google Scholar 

  42. Lampugnani MG, Corada M, Caveda L, Breviario F, Ayalon O, Geiger B, Dejana E (1995) The molecular organization of endothelial cell to cell junctions: differential association of plakoglobin, beta-catenin, and alpha-catenin with vascular endothelial cadherin (VE-cadherin). J Cell Biol 129:203–217

    Article  CAS  PubMed  Google Scholar 

  43. Konstantoulaki M, Kouklis P, Malik AB (2003) Protein kinase C modifications of VE-cadherin, p120, and beta-catenin contribute to endothelial barrier dysregulation induced by thrombin. Am J Physiol Lung Cell Mol Physiol 285:L434–L442

    Article  CAS  PubMed  Google Scholar 

  44. Mehta D, Rahman A, Malik AB (2001) Protein kinase C-alpha signals rho-guanine nucleotide dissociation inhibitor phosphorylation and rho activation and regulates the endothelial cell barrier function. J Biol Chem 276:22614–22620

    Article  CAS  PubMed  Google Scholar 

  45. Minshall RD, Vandenbroucke EE, Holinstat M, Place AT, Tiruppathi C, Vogel SM, van Nieuw Amerongen GP, Mehta D, Malik AB (2010) Role of protein kinase Czeta in thrombin-induced RhoA activation and inter-endothelial gap formation of human dermal microvessel endothelial cell monolayers. Microvasc Res 80:240–249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Komarova YA, Huang F, Geyer M, Daneshjou N, Garcia A, Idalino L, Kreutz B, Mehta D, Malik AB (2012) VE-cadherin signaling induces EB3 phosphorylation to suppress microtubule growth and assemble adherens junctions. Mol Cell 48:914–925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Vandenbroucke St Amant E, Tauseef M, Vogel SM, Gao XP, Mehta D, Komarova YA, Malik AB (2012) PKCalpha activation of p120-catenin serine 879 phospho-switch disassembles VE-cadherin junctions and disrupts vascular integrity. Circ Res 111:739–749

    Article  CAS  PubMed  Google Scholar 

  48. Nguyen LT, Lum H, Tiruppathi C, Malik AB (1997) Site-specific thrombin receptor antibodies inhibit Ca2+ signaling and increased endothelial permeability. Am J Physiol 273:C1756–C1763

    CAS  PubMed  Google Scholar 

  49. Singh I, Knezevic N, Ahmmed GU, Kini V, Malik AB, Mehta D (2007) Galphaq-TRPC6-mediated Ca2+ entry induces RhoA activation and resultant endothelial cell shape change in response to thrombin. J Biol Chem 282:7833–7843

    Article  CAS  PubMed  Google Scholar 

  50. Kini V, Chavez A, Mehta D (2010) A new role for PTEN in regulating transient receptor potential canonical channel 6-mediated Ca2+ entry, endothelial permeability, and angiogenesis. J Biol Chem 285:33082–33091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Tauseef M, Knezevic N, Chava KR, Smith M, Sukriti S, Gianaris N, Obukhov AG, Vogel SM, Schraufnagel DE, Dietrich A, Birnbaumer L, Malik AB, Mehta D (2012) TLR4 activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation. J Exp Med 209:1953–1968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gandhirajan RK, Meng S, Chandramoorthy HC, Mallilankaraman K, Mancarella S, Gao H, Razmpour R, Yang XF, Houser SR, Chen J, Koch WJ, Wang H, Soboloff J, Gill DL et al (2013) Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation. J Clin Investig 123:887–902

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Geyer M, Huang F, Sun Y, Vogel SM, Malik AB, Taylor CW, Komarova YA (2015) Microtubule-associated protein EB3 regulates IP3 receptor clustering and Ca(2+) signaling in endothelial cells. Cell Rep 12:79–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lewit-Bentley A, Rety S (2000) EF-hand calcium-binding proteins. Curr Opin Struct Biol 10:637–643

    Article  CAS  PubMed  Google Scholar 

  55. Kretsinger RH, Nockolds CE (1973) Carp muscle calcium-binding protein. II. Structure determination and general description. J Biol Chem 248:3313–3326

    CAS  PubMed  Google Scholar 

  56. Nelson MR, Chazin WJ (1998) An interaction-based analysis of calcium-induced conformational changes in Ca2+ sensor proteins. Protein Sci 7:270–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Maler L, Blankenship J, Rance M, Chazin WJ (2000) Site-site communication in the EF-hand Ca2+-binding protein calbindin D9k. Nat Struct Biol 7:245–250

    Article  CAS  PubMed  Google Scholar 

  58. Borbiev T, Verin AD, Shi S, Liu F, Garcia JG (2001) Regulation of endothelial cell barrier function by calcium/calmodulin-dependent protein kinase II. Am J Physiol Lung Cell Mol Physiol 280:L983–L990

    CAS  PubMed  Google Scholar 

  59. Sandoval R, Malik AB, Minshall RD, Kouklis P, Ellis CA, Tiruppathi C (2001) Ca(2+) signalling and PKCalpha activate increased endothelial permeability by disassembly of VE-cadherin junctions. J Physiol 533:433–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Borbiev T, Verin AD, Birukova A, Liu F, Crow MT, Garcia JG (2003) Role of CaM kinase II and ERK activation in thrombin-induced endothelial cell barrier dysfunction. Am J Physiol Lung Cell Mol Physiol 285:L43–L54

    Article  CAS  PubMed  Google Scholar 

  61. Wainwright MS, Rossi J, Schavocky J, Crawford S, Steinhorn D, Velentza AV, Zasadzki M, Shirinsky V, Jia Y, Haiech J, Van Eldik LJ, Watterson DM (2003) Protein kinase involved in lung injury susceptibility: evidence from enzyme isoform genetic knockout and in vivo inhibitor treatment. Proc Natl Acad Sci USA 100:6233–6238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Peng J, He F, Zhang C, Deng X, Yin F (2011) Protein kinase C-alpha signals P115RhoGEF phosphorylation and RhoA activation in TNF-alpha-induced mouse brain microvascular endothelial cell barrier dysfunction. J Neuroinflammation 8:28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Wang Z, Ginnan R, Abdullaev IF, Trebak M, Vincent PA, Singer HA (2010) Calcium/calmodulin-dependent protein kinase II delta 6 (CaMKIIdelta6) and RhoA involvement in thrombin-induced endothelial barrier dysfunction. J Biol Chem 285:21303–21312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Xie L, Chiang ET, Wu X, Kelly GT, Kanteti P, Singleton PA, Camp SM, Zhou T, Dudek SM, Natarajan V, Wang T, Black SM, Garcia JG, Jacobson JR (2016) Regulation of thrombin-induced lung endothelial cell barrier disruption by protein kinase C delta. PLoS One 11:e0158865

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Xia X, Mariner DJ, Reynolds AB (2003) Adhesion-associated and PKC-modulated changes in serine/threonine phosphorylation of p120-catenin. Biochemistry 42:9195–9204

    Article  CAS  PubMed  Google Scholar 

  66. Brown MV, Burnett PE, Denning MF, Reynolds AB (2009) PDGF receptor activation induces p120-catenin phosphorylation at serine 879 via a PKCalpha-dependent pathway. Exp Cell Res 315:39–49

    Article  CAS  PubMed  Google Scholar 

  67. Xiao K, Garner J, Buckley KM, Vincent PA, Chiasson CM, Dejana E, Faundez V, Kowalczyk AP (2005) p120-Catenin regulates clathrin-dependent endocytosis of VE-cadherin. Mol Biol Cell 16:5141–5151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Chiasson CM, Wittich KB, Vincent PA, Faundez V, Kowalczyk AP (2009) p120-catenin inhibits VE-cadherin internalization through a Rho-independent mechanism. Mol Biol Cell 20:1970–1980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Nanes BA, Chiasson-MacKenzie C, Lowery AM, Ishiyama N, Faundez V, Ikura M, Vincent PA, Kowalczyk AP (2012) p120-catenin binding masks an endocytic signal conserved in classical cadherins. J Cell Biol 199:365–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Nanes BA, Grimsley-Myers CM, Cadwell CM, Robinson BS, Lowery AM, Vincent PA, Mosunjac M, Fruh K, Kowalczyk AP (2017) p120-catenin regulates VE-cadherin endocytosis and degradation induced by the Kaposi sarcoma-associated ubiquitin ligase K5. Mol Biol Cell 28:30–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Su W, Kowalczyk AP (2017) The VE-cadherin cytoplasmic domain undergoes proteolytic processing during endocytosis. Mol Biol Cell 28:76–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Nakano K, Takaishi K, Kodama A, Mammoto A, Shiozaki H, Monden M, Takai Y (1999) Distinct actions and cooperative roles of ROCK and mDia in Rho small G protein-induced reorganization of the actin cytoskeleton in Madin–Darby canine kidney cells. Mol Biol Cell 10:2481–2491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Geneste O, Copeland JW, Treisman R (2002) LIM kinase and Diaphanous cooperate to regulate serum response factor and actin dynamics. J Cell Biol 157:831–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Tsuji T, Ishizaki T, Okamoto M, Higashida C, Kimura K, Furuyashiki T, Arakawa Y, Birge RB, Nakamoto T, Hirai H, Narumiya S (2002) ROCK and mDia1 antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts. J Cell Biol 157:819–830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Knezevic N, Roy A, Timblin B, Konstantoulaki M, Sharma T, Malik AB, Mehta D (2007) GDI-1 phosphorylation switch at serine 96 induces RhoA activation and increased endothelial permeability. Mol Cell Biol 27:6323–6333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Holinstat M, Mehta D, Kozasa T, Minshall RD, Malik AB (2003) Protein kinase Calpha-induced p115RhoGEF phosphorylation signals endothelial cytoskeletal rearrangement. J Biol Chem 278:28793–28798

    Article  CAS  PubMed  Google Scholar 

  77. Dubash AD, Wennerberg K, Garcia-Mata R, Menold MM, Arthur WT, Burridge K (2007) A novel role for Lsc/p115 RhoGEF and LARG in regulating RhoA activity downstream of adhesion to fibronectin. J Cell Sci 120:3989–3998

    Article  CAS  PubMed  Google Scholar 

  78. Chow CR, Suzuki N, Kawamura T, Hamakubo T, Kozasa T (2013) Modification of p115RhoGEF Ser(330) regulates its RhoGEF activity. Cell Signal 25:2085–2092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Feng J, Ito M, Ichikawa K, Isaka N, Nishikawa M, Hartshorne DJ, Nakano T (1999) Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase. J Biol Chem 274:37385–37390

    Article  CAS  PubMed  Google Scholar 

  80. van Nieuw Amerongen GP, van Delft S, Vermeer MA, Collard JG, van Hinsbergh VW (2000) Activation of RhoA by thrombin in endothelial hyperpermeability: role of Rho kinase and protein tyrosine kinases. Circ Res 87:335–340

    Article  PubMed  Google Scholar 

  81. Fukata M, Kaibuchi K (2001) Rho-family GTPases in cadherin-mediated cell–cell adhesion. Nat Rev Mol Cell Biol 2:887–897

    Article  CAS  PubMed  Google Scholar 

  82. Craig R, Smith R, Kendrick-Jones J (1983) Light-chain phosphorylation controls the conformation of vertebrate non-muscle and smooth muscle myosin molecules. Nature 302:436–439

    Article  CAS  PubMed  Google Scholar 

  83. Allen BG, Walsh MP (1994) The biochemical basis of the regulation of smooth-muscle contraction. Trends Biochem Sci 19:362–368

    Article  CAS  PubMed  Google Scholar 

  84. Shimokawa H, Seto M, Katsumata N, Amano M, Kozai T, Yamawaki T, Kuwata K, Kandabashi T, Egashira K, Ikegaki I, Asano T, Kaibuchi K, Takeshita A (1999) Rho-kinase-mediated pathway induces enhanced myosin light chain phosphorylations in a swine model of coronary artery spasm. Cardiovasc Res 43:1029–1039

    Article  CAS  PubMed  Google Scholar 

  85. Herzog D, Loetscher P, van Hengel J, Knusel S, Brakebusch C, Taylor V, Suter U, Relvas JB (2011) The small GTPase RhoA is required to maintain spinal cord neuroepithelium organization and the neural stem cell pool. J Neurosci 31:5120–5130

    Article  CAS  PubMed  Google Scholar 

  86. Nawroth R, Poell G, Ranft A, Kloep S, Samulowitz U, Fachinger G, Golding M, Shima DT, Deutsch U, Vestweber D (2002) VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts. EMBO J 21:4885–4895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Baumer S, Keller L, Holtmann A, Funke R, August B, Gamp A, Wolburg H, Wolburg-Buchholz K, Deutsch U, Vestweber D (2006) Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development. Blood 107:4754–4762

    Article  PubMed  CAS  Google Scholar 

  88. Gong H, Rehman J, Tang H, Wary K, Mittal M, Chaturvedi P, Zhao YY, Komarova YA, Vogel SM, Malik AB (2015) HIF2alpha signaling inhibits adherens junctional disruption in acute lung injury. J Clin Investig 125:652–664

    Article  PubMed  PubMed Central  Google Scholar 

  89. Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, Malik AB, Tiruppathi C (2017) Pyk2 phosphorylation of VE-PTP downstream of STIM1-induced Ca2+ entry regulates disassembly of adherens junctions. Am J Physiol Lung Cell Mol Physiol 312:L1003–L1017

    Article  PubMed  Google Scholar 

  90. 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 169:435–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. 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 15:1235–1241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Yazbeck P, Tauseef M, Kruse K, Amin MR, Sheikh R, Feske S, Komarova Y, Mehta D (2017) STIM1 phosphorylation at Y361 recruits Orai1 to STIM1 puncta and induces Ca2+ entry. Sci Rep 7:42758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Stolwijk JA, Zhang X, Gueguinou M, Zhang W, Matrougui K, Renken C, Trebak M (2016) Calcium signaling is dispensable for receptor regulation of endothelial barrier function. J Biol Chem 291:22894–22912

    Article  CAS  PubMed  Google Scholar 

  94. Clipstone NA, Crabtree GR (1992) Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature 357:695–697

    Article  CAS  PubMed  Google Scholar 

  95. Klee CB, Crouch TH, Krinks MH (1979) Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proc Natl Acad Sci USA 76:6270–6273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Vasauskas AA, Chen H, Wu S, Cioffi DL (2014) The serine-threonine phosphatase calcineurin is a regulator of endothelial store-operated calcium entry. Pulm Circ 4:116–127

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Jain J, McCaffrey PG, Miner Z, Kerppola TK, Lambert JN, Verdine GL, Curran T, Rao A (1993) The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun. Nature 365:352–355

    Article  CAS  PubMed  Google Scholar 

  98. Crabtree GR, Olson EN (2002) NFAT signaling: choreographing the social lives of cells. Cell 109(Suppl):S67–S79

    Article  CAS  PubMed  Google Scholar 

  99. Clapham DE (2007) Calcium signaling. Cell 131:1047–1058

    Article  CAS  PubMed  Google Scholar 

  100. Wood PG, Gillespie JI (1998) Evidence for mitochondrial Ca(2+)-induced Ca2+ release in permeabilised endothelial cells. Biochem Biophys Res Commun 246:543–548

    Article  CAS  PubMed  Google Scholar 

  101. Suzuki J, Kanemaru K, Ishii K, Ohkura M, Okubo Y, Iino M (2014) Imaging intraorganellar Ca2+ at subcellular resolution using CEPIA. Nat Commun 5:4153

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Carafoli E, Crompton M (1978) The regulation of intracellular calcium by mitochondria. Ann N Y Acad Sci 307:269–284

    Article  CAS  PubMed  Google Scholar 

  103. Katz AM, Repke DI, Fudyma G, Shigekawa M (1977) Control of calcium efflux from sarcoplasmic reticulum vesicles by external calcium. J Biol Chem 252:4210–4214

    CAS  PubMed  Google Scholar 

  104. Docampo R, Huang G (2016) Acidocalcisomes of eukaryotes. Curr Opin Cell Biol 41:66–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Domotor E, Abbott NJ, Adam-Vizi V (1999) Na+–Ca2+ exchange and its implications for calcium homeostasis in primary cultured rat brain microvascular endothelial cells. J Physiol 515(Pt 1):147–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Moccia F, Berra-Romani R, Baruffi S, Spaggiari S, Signorelli S, Castelli L, Magistretti J, Taglietti V, Tanzi F (2002) Ca2+ uptake by the endoplasmic reticulum Ca2+-ATPase in rat microvascular endothelial cells. Biochem J 364:235–244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Wang X, Reznick S, Li P, Liang W, van Breemen C (2002) Ca(2+) removal mechanisms in freshly isolated rabbit aortic endothelial cells. Cell Calcium 31:265–277

    Article  CAS  PubMed  Google Scholar 

  108. Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4:517–529

    Article  CAS  PubMed  Google Scholar 

  109. Patel A, Sharif-Naeini R, Folgering JR, Bichet D, Duprat F, Honore E (2010) Canonical TRP channels and mechanotransduction: from physiology to disease states. Pflugers Arch 460:571–581

    Article  CAS  PubMed  Google Scholar 

  110. Zhu MX, Ma J, Parrington J, Calcraft PJ, Galione A, Evans AM (2010) Calcium signaling via two-pore channels: local or global, that is the question. Am J Physiol Cell Physiol 298:C430–C441

    Article  CAS  PubMed  Google Scholar 

  111. Ambudkar IS, de Souza LB, Ong HL (2016) TRPC1, Orai1, and STIM1 in SOCE: friends in tight spaces. Cell Calcium. doi:10.1016/j.ceca.2016.12.009

    Google Scholar 

  112. Toyoshima C, Cornelius F (2013) New crystal structures of PII-type ATPases: excitement continues. Curr Opin Struct Biol 23:507–514

    Article  CAS  PubMed  Google Scholar 

  113. Moller JV, Juul B, le Maire M (1996) Structural organization, ion transport, and energy transduction of P-type ATPases. Biochim Biophys Acta 1286:1–51

    Article  PubMed  Google Scholar 

  114. Hilgemann DW, Yaradanakul A, Wang Y, Fuster D (2006) Molecular control of cardiac sodium homeostasis in health and disease. J Cardiovasc Electrophysiol 17(Suppl 1):S47–S56

    Article  PubMed  Google Scholar 

  115. Niggli V, Sigel E, Carafoli E (1982) The purified Ca2+ pump of human erythrocyte membranes catalyzes an electroneutral Ca2+–H+ exchange in reconstituted liposomal systems. J Biol Chem 257:2350–2356

    CAS  PubMed  Google Scholar 

  116. Smallwood JI, Waisman DM, Lafreniere D, Rasmussen H (1983) Evidence that the erythrocyte calcium pump catalyzes a Ca2+:nH+ exchange. J Biol Chem 258:11092–11097

    CAS  PubMed  Google Scholar 

  117. Sweadner KJ, Donnet C (2001) Structural similarities of Na, K-ATPase and SERCA, the Ca(2+)-ATPase of the sarcoplasmic reticulum. Biochem J 356:685–704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Furuichi T, Yoshikawa S, Miyawaki A, Wada K, Maeda N, Mikoshiba K (1989) Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400. Nature 342:32–38

    Article  CAS  PubMed  Google Scholar 

  119. Mikoshiba K, Changeux JP (1978) Morphological and biochemical studies on isolated molecular and granular layers from bovine cerebellum. Brain Res 142:487–504

    Article  CAS  PubMed  Google Scholar 

  120. Streb H, Irvine RF, Berridge MJ, Schulz I (1983) Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature 306:67–69

    Article  CAS  PubMed  Google Scholar 

  121. Pessah IN, Francini AO, Scales DJ, Waterhouse AL, Casida JE (1986) Calcium-ryanodine receptor complex. Solubilization and partial characterization from skeletal muscle junctional sarcoplasmic reticulum vesicles. J Biol Chem 261:8643–8648

    CAS  PubMed  Google Scholar 

  122. Inui M, Saito A, Fleischer S (1987) Isolation of the ryanodine receptor from cardiac sarcoplasmic reticulum and identity with the feet structures. J Biol Chem 262:15637–15642

    CAS  PubMed  Google Scholar 

  123. Inui M, Saito A, Fleischer S (1987) Purification of the ryanodine receptor and identity with feet structures of junctional terminal cisternae of sarcoplasmic reticulum from fast skeletal muscle. J Biol Chem 262:1740–1747

    CAS  PubMed  Google Scholar 

  124. Mauger JP, Claret M, Pietri F, Hilly M (1989) Hormonal regulation of inositol 1,4,5-trisphosphate receptor in rat liver. J Biol Chem 264:8821–8826

    CAS  PubMed  Google Scholar 

  125. Chadwick CC, Saito A, Fleischer S (1990) Isolation and characterization of the inositol trisphosphate receptor from smooth muscle. Proc Natl Acad Sci USA 87:2132–2136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Seo MD, Velamakanni S, Ishiyama N, Stathopulos PB, Rossi AM, Khan SA, Dale P, Li C, Ames JB, Ikura M, Taylor CW (2012) Structural and functional conservation of key domains in InsP3 and ryanodine receptors. Nature 483:108–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Moccia F, Berra-Romani R, Tanzi F (2012) Update on vascular endothelial Ca(2+) signalling: a tale of ion channels, pumps and transporters. World J Biol Chem 3:127–158

    Article  PubMed  PubMed Central  Google Scholar 

  128. Prole DL, Taylor CW (2016) Inositol 1,4,5-trisphosphate receptors and their protein partners as signalling hubs. J Physiol 594:2849–2866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Supattapone S, Worley PF, Baraban JM, Snyder SH (1988) Solubilization, purification, and characterization of an inositol trisphosphate receptor. J Biol Chem 263:1530–1534

    CAS  PubMed  Google Scholar 

  130. Jiang QX, Thrower EC, Chester DW, Ehrlich BE, Sigworth FJ (2002) Three-dimensional structure of the type 1 inositol 1,4,5-trisphosphate receptor at 24 A resolution. EMBO J 21:3575–3581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Taylor CW, Genazzani AA, Morris SA (1999) Expression of inositol trisphosphate receptors. Cell Calcium 26:237–251

    Article  CAS  PubMed  Google Scholar 

  132. Parys JB, Sernett SW, DeLisle S, Snyder PM, Welsh MJ, Campbell KP (1992) Isolation, characterization, and localization of the inositol 1,4,5-trisphosphate receptor protein in Xenopus laevis oocytes. J Biol Chem 267:18776–18782

    CAS  PubMed  Google Scholar 

  133. Fan G, Baker ML, Wang Z, Baker MR, Sinyagovskiy PA, Chiu W, Ludtke SJ, Serysheva II (2015) Gating machinery of InsP3R channels revealed by electron cryomicroscopy. Nature 527:336–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Sheppard CA, Simpson PB, Sharp AH, Nucifora FC, Ross CA, Lange GD, Russell JT (1997) Comparison of type 2 inositol 1,4,5-trisphosphate receptor distribution and subcellular Ca2+ release sites that support Ca2+ waves in cultured astrocytes. J Neurochem 68:2317–2327

    Article  CAS  PubMed  Google Scholar 

  135. Iwai M, Tateishi Y, Hattori M, Mizutani A, Nakamura T, Futatsugi A, Inoue T, Furuichi T, Michikawa T, Mikoshiba K (2005) Molecular cloning of mouse type 2 and type 3 inositol 1,4,5-trisphosphate receptors and identification of a novel type 2 receptor splice variant. J Biol Chem 280:10305–10317

    Article  CAS  PubMed  Google Scholar 

  136. Mak DO, Foskett JK (1997) Single-channel kinetics, inactivation, and spatial distribution of inositol trisphosphate (IP3) receptors in Xenopus oocyte nucleus. J Gen Physiol 109:571–587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Cruttwell C, Bernard J, Hilly M, Nicolas V, Tunwell RE, Mauger JP (2005) Dynamics of the Ins(1,4,5)P3 receptor during polarization of MDCK cells. Biol Cell 97:699–707

    Article  CAS  PubMed  Google Scholar 

  138. Chalmers M, Schell MJ, Thorn P (2006) Agonist-evoked inositol trisphosphate receptor (IP3R) clustering is not dependent on changes in the structure of the endoplasmic reticulum. Biochem J 394:57–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Pantazaka E, Taylor CW (2011) Differential distribution, clustering, and lateral diffusion of subtypes of the inositol 1,4,5-trisphosphate receptor. J Biol Chem 286:23378–23387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Smith IF, Swaminathan D, Dickinson GD, Parker I (2014) Single-molecule tracking of inositol trisphosphate receptors reveals different motilities and distributions. Biophys J 107:834–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Rahman T, Skupin A, Falcke M, Taylor CW (2009) Clustering of InsP3 receptors by InsP3 retunes their regulation by InsP3 and Ca2+. Nature 458:655–659

    Article  Google Scholar 

  142. Rahman T (2012) Dynamic clustering of IP3 receptors by IP3. Biochem Soc Trans 40:325–330

    Article  CAS  PubMed  Google Scholar 

  143. Taylor SJ, Chae HZ, Rhee SG, Exton JH (1991) Activation of the beta 1 isozyme of phospholipase C by alpha subunits of the Gq class of G proteins. Nature 350:516–518

    Article  CAS  PubMed  Google Scholar 

  144. Smrcka AV, Hepler JR, Brown KO, Sternweis PC (1991) Regulation of polyphosphoinositide-specific phospholipase C activity by purified Gq. Science 251:804–807

    Article  CAS  PubMed  Google Scholar 

  145. Suh PG, Park JI, Manzoli L, Cocco L, Peak JC, Katan M, Fukami K, Kataoka T, Yun S, Ryu SH (2008) Multiple roles of phosphoinositide-specific phospholipase C isozymes. BMB Rep 41:415–434

    Article  CAS  PubMed  Google Scholar 

  146. Beziau DM, Toussaint F, Blanchette A, Dayeh NR, Charbel C, Tardif JC, Dupuis J, Ledoux J (2015) Expression of phosphoinositide-specific phospholipase C isoforms in native endothelial cells. PLoS One 10:e0123769

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Ji QS, Winnier GE, Niswender KD, Horstman D, Wisdom R, Magnuson MA, Carpenter G (1997) Essential role of the tyrosine kinase substrate phospholipase C-gamma1 in mammalian growth and development. Proc Natl Acad Sci USA 94:2999–3003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Liao HJ, Kume T, McKay C, Xu MJ, Ihle JN, Carpenter G (2002) Absence of erythrogenesis and vasculogenesis in Plcg1-deficient mice. J Biol Chem 277:9335–9341

    Article  CAS  PubMed  Google Scholar 

  149. Muldowney JA 3rd, Painter CA, Sanders-Bush E, Brown NJ, Vaughan DE (2007) Acute tissue-type plasminogen activator release in human microvascular endothelial cells: the roles of Galphaq, PLC-beta, IP3 and 5,6-epoxyeicosatrienoic acid. Thromb Haemost 97:263–271

    CAS  PubMed  Google Scholar 

  150. Seehaus S, Shahzad K, Kashif M, Vinnikov IA, Schiller M, Wang H, Madhusudhan T, Eckstein V, Bierhaus A, Bea F, Blessing E, Weiler H, Frommhold D, Nawroth PP et al (2009) Hypercoagulability inhibits monocyte transendothelial migration through protease-activated receptor-1-, phospholipase-Cbeta-, phosphoinositide 3-kinase-, and nitric oxide-dependent signaling in monocytes and promotes plaque stability. Circulation 120:774–784

    Article  CAS  PubMed  Google Scholar 

  151. Nussbaum C, Bannenberg S, Keul P, Graler MH, Goncalves-de-Albuquerque CF, Korhonen H, von Wnuck Lipinski K, Heusch G, de Castro Faria Neto HC, Rohwedder I, Gothert JR, Prasad VP, Haufe G, Lange-Sperandio B et al (2015) Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin. Nat Commun 6:6416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Mikelis CM, Simaan M, Ando K, Fukuhara S, Sakurai A, Amornphimoltham P, Masedunskas A, Weigert R, Chavakis T, Adams RH, Offermanns S, Mochizuki N, Zheng Y, Gutkind JS (2015) RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock. Nat Commun 6:6725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Hoeppner LH, Phoenix KN, Clark KJ, Bhattacharya R, Gong X, Sciuto TE, Vohra P, Suresh S, Bhattacharya S, Dvorak AM, Ekker SC, Dvorak HF, Claffey KP, Mukhopadhyay D (2012) Revealing the role of phospholipase Cbeta3 in the regulation of VEGF-induced vascular permeability. Blood 120:2167–2173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Bezprozvanny I, Watras J, Ehrlich BE (1991) Bell-shaped calcium-response curves of Ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum. Nature 351:751–754

    Article  CAS  PubMed  Google Scholar 

  155. Mak DO, McBride S, Foskett JK (1998) Inositol 1,4,5-trisphosphate [correction of tris-phosphate] activation of inositol trisphosphate [correction of tris-phosphate] receptor Ca2+ channel by ligand tuning of Ca2+ inhibition. Proc Natl Acad Sci USA 95:15821–15825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Iino M (1990) Biphasic Ca2+ dependence of inositol 1,4,5-trisphosphate-induced Ca release in smooth muscle cells of the guinea pig taenia caeci. J Gen Physiol 95:1103–1122

    Article  CAS  PubMed  Google Scholar 

  157. Finch EA, Turner TJ, Goldin SM (1991) Calcium as a coagonist of inositol 1,4,5-trisphosphate-induced calcium release. Science 252:443–446

    Article  CAS  PubMed  Google Scholar 

  158. Marshall IC, Taylor CW (1993) Biphasic effects of cytosolic Ca2+ on Ins(1,4,5)P3-stimulated Ca2+ mobilization in hepatocytes. J Biol Chem 268:13214–13220

    CAS  PubMed  Google Scholar 

  159. Parys JB, Missiaen L, De Smedt H, Casteels R (1993) Loading dependence of inositol 1,4,5-trisphosphate-induced Ca2+ release in the clonal cell line A7r5. Implications for the mechanism of quantal Ca2+ release. J Biol Chem 268:25206–25212

    CAS  PubMed  Google Scholar 

  160. Sienaert I, De Smedt H, Parys JB, Missiaen L, Vanlingen S, Sipma H, Casteels R (1996) Characterization of a cytosolic and a luminal Ca2+ binding site in the type I inositol 1,4,5-trisphosphate receptor. J Biol Chem 271:27005–27012

    Article  CAS  PubMed  Google Scholar 

  161. Sienaert I, Missiaen L, De Smedt H, Parys JB, Sipma H, Casteels R (1997) Molecular and functional evidence for multiple Ca2+-binding domains in the type 1 inositol 1,4,5-trisphosphate receptor. J Biol Chem 272:25899–25906

    Article  CAS  PubMed  Google Scholar 

  162. Miyakawa T, Mizushima A, Hirose K, Yamazawa T, Bezprozvanny I, Kurosaki T, Iino M (2001) Ca(2+)-sensor region of IP(3) receptor controls intracellular Ca(2+) signaling. EMBO J 20:1674–1680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Tu H, Nosyreva E, Miyakawa T, Wang Z, Mizushima A, Iino M, Bezprozvanny I (2003) Functional and biochemical analysis of the type 1 inositol (1,4,5)-trisphosphate receptor calcium sensor. Biophys J 85:290–299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Joseph SK, Brownell S, Khan MT (2005) Calcium regulation of inositol 1,4,5-trisphosphate receptors. Cell Calcium 38:539–546

    Article  CAS  PubMed  Google Scholar 

  165. Berridge MJ (2007) Inositol trisphosphate and calcium oscillations. Biochem Soc Symp 74:1–7

    Article  CAS  Google Scholar 

  166. Patel S, Morris SA, Adkins CE, O’Beirne G, Taylor CW (1997) Ca2+-independent inhibition of inositol trisphosphate receptors by calmodulin: redistribution of calmodulin as a possible means of regulating Ca2+ mobilization. Proc Natl Acad Sci USA 94:11627–11632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Adkins CE, Morris SA, De Smedt H, Sienaert I, Torok K, Taylor CW (2000) Ca2+-calmodulin inhibits Ca2+ release mediated by type-1, -2 and -3 inositol trisphosphate receptors. Biochem J 345(Pt 2):357–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Hirota J, Michikawa T, Natsume T, Furuichi T, Mikoshiba K (1999) Calmodulin inhibits inositol 1,4,5-trisphosphate-induced calcium release through the purified and reconstituted inositol 1,4,5-trisphosphate receptor type 1. FEBS Lett 456:322–326

    Article  CAS  PubMed  Google Scholar 

  169. Missiaen L, DeSmedt H, Bultynck G, Vanlingen S, Desmet P, Callewaert G, Parys JB (2000) Calmodulin increases the sensitivity of type 3 inositol-1,4, 5-trisphosphate receptors to Ca(2+) inhibition in human bronchial mucosal cells. Mol Pharmacol 57:564–567

    CAS  PubMed  Google Scholar 

  170. Kasri NN, Holmes AM, Bultynck G, Parys JB, Bootman MD, Rietdorf K, Missiaen L, McDonald F, De Smedt H, Conway SJ, Holmes AB, Berridge MJ, Roderick HL (2004) Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins. EMBO J 23:312–321

    Article  CAS  PubMed  Google Scholar 

  171. Serysheva II (2014) Toward a high-resolution structure of IP(3)R channel. Cell Calcium 56:125–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Sienaert I, Nadif Kasri N, Vanlingen S, Parys JB, Callewaert G, Missiaen L, de Smedt H (2002) Localization and function of a calmodulin–apocalmodulin-binding domain in the N-terminal part of the type 1 inositol 1,4,5-trisphosphate receptor. Biochem J 365:269–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Fabiato A (1983) Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 245:C1–C14

    CAS  PubMed  Google Scholar 

  174. Takeshima H, Nishimura S, Matsumoto T, Ishida H, Kangawa K, Minamino N, Matsuo H, Ueda M, Hanaoka M, Hirose T et al (1989) Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor. Nature 339:439–445

    Article  CAS  PubMed  Google Scholar 

  175. Cheng H, Lederer WJ, Cannell MB (1993) Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science 262:740–744

    Article  CAS  PubMed  Google Scholar 

  176. des Georges A, Clarke OB, Zalk R, Yuan Q, Condon KJ, Grassucci RA, Hendrickson WA, Marks AR, Frank J (2016) Structural basis for gating and activation of RyR1. Cell 167:145–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Marks AR, Tempst P, Hwang KS, Taubman MB, Inui M, Chadwick C, Fleischer S, Nadal-Ginard B (1989) Molecular cloning and characterization of the ryanodine receptor/junctional channel complex cDNA from skeletal muscle sarcoplasmic reticulum. Proc Natl Acad Sci USA 86:8683–8687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Nakai J, Imagawa T, Hakamat Y, Shigekawa M, Takeshima H, Numa S (1990) Primary structure and functional expression from cDNA of the cardiac ryanodine receptor/calcium release channel. FEBS Lett 271:169–177

    Article  CAS  PubMed  Google Scholar 

  179. Lesh RE, Marks AR, Somlyo AV, Fleischer S, Somlyo AP (1993) Anti-ryanodine receptor antibody binding sites in vascular and endocardial endothelium. Circ Res 72:481–488

    Article  CAS  PubMed  Google Scholar 

  180. Köhler R, Brakemeier S, Kühn M, Degenhardt C, Buhr H, Pries A, Hoyer J (2001) Expression of ryanodine receptor type 3 and TRP channels in endothelial cells: comparison of in situ and cultured human endothelial cells. Cardiovasc Res 51:160–168

    Article  PubMed  Google Scholar 

  181. Edwards GA, Weiant EA, Slocombe AG, Roeder KD (1948) The action of ryanodine on the contractile process in striated muscle. Science 108:330–332

    Article  CAS  PubMed  Google Scholar 

  182. Ciofalo FR (1973) Relationship between 3H-ryanodine uptake and myocardial contractility. Am J Physiol 225:324–327

    CAS  PubMed  Google Scholar 

  183. Nagasaki K, Fleischer S (1988) Ryanodine sensitivity of the calcium release channel of sarcoplasmic reticulum. Cell Calcium 9:1–7

    Article  CAS  PubMed  Google Scholar 

  184. McGrew SG, Wolleben C, Siegl P, Inui M, Fleischer S (1989) Positive cooperativity of ryanodine binding to the calcium release channel of sarcoplasmic reticulum from heart and skeletal muscle. Biochemistry 28:1686–1691

    Article  CAS  PubMed  Google Scholar 

  185. Gyorke S, Fill M (1993) Ryanodine receptor adaptation: control mechanism of Ca(2+)-induced Ca2+ release in heart. Science 260:807–809

    Article  CAS  PubMed  Google Scholar 

  186. Tripathy A, Xu L, Mann G, Meissner G (1995) Calmodulin activation and inhibition of skeletal muscle Ca2+ release channel (ryanodine receptor). Biophys J 69:106–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Lai FA, Misra M, Xu L, Smith HA, Meissner G (1989) The ryanodine receptor-Ca2+ release channel complex of skeletal muscle sarcoplasmic reticulum. Evidence for a cooperatively coupled, negatively charged homotetramer. J Biol Chem 264:16776–16785

    CAS  PubMed  Google Scholar 

  188. Ziegelstein RC, Spurgeon HA, Pili R, Passaniti A, Cheng L, Corda S, Lakatta EG, Capogrossi MC (1994) A functional ryanodine-sensitive intracellular Ca2+ store is present in vascular endothelial cells. Circ Res 74:151–156

    Article  CAS  PubMed  Google Scholar 

  189. Seo MD, Enomoto M, Ishiyama N, Stathopulos PB, Ikura M (2015) Structural insights into endoplasmic reticulum stored calcium regulation by inositol 1,4,5-trisphosphate and ryanodine receptors. Biochim Biophys Acta 1853:1980–1991

    Article  CAS  PubMed  Google Scholar 

  190. Van Petegem F (2015) Ryanodine receptors: allosteric ion channel giants. J Mol Biol 427:31–53

    Article  PubMed  CAS  Google Scholar 

  191. Clarke OB, Hendrickson WA (2016) Structures of the colossal RyR1 calcium release channel. Curr Opin Struct Biol 39:144–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Calcraft PJ, Ruas M, Pan Z, Cheng X, Arredouani A, Hao X, Tang J, Rietdorf K, Teboul L, Chuang KT, Lin P, Xiao R, Wang C, Zhu Y et al (2009) NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 459:596–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Favia A, Desideri M, Gambara G, D’Alessio A, Ruas M, Esposito B, Del Bufalo D, Parrington J, Ziparo E, Palombi F, Galione A, Filippini A (2014) VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2-dependent Ca2+ signaling. Proc Natl Acad Sci USA 111:E4706–E4715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Zuccolo E, Dragoni S, Poletto V, Catarsi P, Guido D, Rappa A, Reforgiato M, Lodola F, Lim D, Rosti V, Guerra G, Moccia F (2016) Arachidonic acid-evoked Ca2+ signals promote nitric oxide release and proliferation in human endothelial colony forming cells. Vascul Pharmacol 87:159–171

    Article  CAS  PubMed  Google Scholar 

  195. Brailoiu E, Churamani D, Cai X, Schrlau MG, Brailoiu GC, Gao X, Hooper R, Boulware MJ, Dun NJ, Marchant JS, Patel S (2009) Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling. J Cell Biol 186:201–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Ruas M, Rietdorf K, Arredouani A, Davis LC, Lloyd-Evans E, Koegel H, Funnell TM, Morgan AJ, Ward JA, Watanabe K, Cheng X, Churchill GC, Zhu MX, Platt FM et al (2010) Purified TPC isoforms form NAADP receptors with distinct roles for Ca(2+) signaling and endolysosomal trafficking. Curr Biol 20:703–709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Cang C, Aranda K, Ren D (2014) A non-inactivating high-voltage-activated two-pore Na(+) channel that supports ultra-long action potentials and membrane bistability. Nat Commun 5:5015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Brailoiu E, Hooper R, Cai X, Brailoiu GC, Keebler MV, Dun NJ, Marchant JS, Patel S (2010) An ancestral deuterostome family of two-pore channels mediates nicotinic acid adenine dinucleotide phosphate-dependent calcium release from acidic organelles. J Biol Chem 285:2897–2901

    Article  CAS  PubMed  Google Scholar 

  199. Guo J, Zeng W, Chen Q, Lee C, Chen L, Yang Y, Cang C, Ren D, Jiang Y (2016) Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana. Nature 531:196–201

    Article  CAS  PubMed  Google Scholar 

  200. Ross CA, Danoff SK, Schell MJ, Snyder SH, Ullrich A (1992) Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and differential localization in brain and peripheral tissues. Proc Natl Acad Sci USA 89:4265–4269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Mignery GA, Sudhof TC, Takei K, De Camilli P (1989) Putative receptor for inositol 1,4,5-trisphosphate similar to ryanodine receptor. Nature 342:192–195

    Article  CAS  PubMed  Google Scholar 

  202. Blondel O, Moody MM, Depaoli AM, Sharp AH, Ross CA, Swift H, Bell GI (1994) Localization of inositol trisphosphate receptor subtype 3 to insulin and somatostatin secretory granules and regulation of expression in islets and insulinoma cells. Proc Natl Acad Sci USA 91:7777–7781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Miyakawa T, Maeda A, Yamazawa T, Hirose K, Kurosaki T, Iino M (1999) Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes. EMBO J 18:1303–1308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Nerou EP, Riley AM, Potter BV, Taylor CW (2001) Selective recognition of inositol phosphates by subtypes of the inositol trisphosphate receptor. Biochem J 355:59–69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Chandrasekhar R, Alzayady KJ, Wagner LE 2nd, Yule DI (2016) Unique regulatory properties of heterotetrameric inositol 1,4,5-trisphosphate receptors revealed by studying concatenated receptor constructs. J Biol Chem 291:4846–4860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Iwai M, Michikawa T, Bosanac I, Ikura M, Mikoshiba K (2007) Molecular basis of the isoform-specific ligand-binding affinity of inositol 1,4,5-trisphosphate receptors. J Biol Chem 282:12755–12764

    Article  CAS  PubMed  Google Scholar 

  207. Ramos-Franco J, Fill M, Mignery GA (1998) Isoform-specific function of single inositol 1,4,5-trisphosphate receptor channels. Biophys J 75:834–839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Inoue M, Lin H, Imanaga I, Ogawa K, Warashina A (2004) InsP3 receptor type 2 and oscillatory and monophasic Ca2+ transients in rat adrenal chromaffin cells. Cell Calcium 35:59–70

    Article  CAS  PubMed  Google Scholar 

  209. Tu H, Wang Z, Nosyreva E, De Smedt H, Bezprozvanny I (2005) Functional characterization of mammalian inositol 1,4,5-trisphosphate receptor isoforms. Biophys J 88:1046–1055

    Article  CAS  PubMed  Google Scholar 

  210. Cameron AM, Steiner JP, Roskams AJ, Ali SM, Ronnett GV, Snyder SH (1995) Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12 complex modulates Ca2+ flux. Cell 83:463–472

    Article  CAS  PubMed  Google Scholar 

  211. Smaili SS, Stellato KA, Burnett P, Thomas AP, Gaspers LD (2001) Cyclosporin A inhibits inositol 1,4,5-trisphosphate-dependent Ca2+ signals by enhancing Ca2+ uptake into the endoplasmic reticulum and mitochondria. J Biol Chem 276:23329–23340

    Article  CAS  PubMed  Google Scholar 

  212. Carmody M, Mackrill JJ, Sorrentino V, O’Neill C (2001) FKBP12 associates tightly with the skeletal muscle type 1 ryanodine receptor, but not with other intracellular calcium release channels. FEBS Lett 505:97–102

    Article  CAS  PubMed  Google Scholar 

  213. Salanova M, Priori G, Barone V, Intravaia E, Flucher B, Ciruela F, McIlhinney RA, Parys JB, Mikoshiba K, Sorrentino V (2002) Homer proteins and InsP(3) receptors co-localise in the longitudinal sarcoplasmic reticulum of skeletal muscle fibres. Cell Calcium 32:193–200

    Article  CAS  PubMed  Google Scholar 

  214. Bruce JI, Shuttleworth TJ, Giovannucci DR, Yule DI (2002) Phosphorylation of inositol 1,4,5-trisphosphate receptors in parotid acinar cells. A mechanism for the synergistic effects of cAMP on Ca2+ signaling. J Biol Chem 277:1340–1348

    Article  CAS  PubMed  Google Scholar 

  215. Straub SV, Giovannucci DR, Bruce JI, Yule DI (2002) A role for phosphorylation of inositol 1,4,5-trisphosphate receptors in defining calcium signals induced by peptide agonists in pancreatic acinar cells. J Biol Chem 277:31949–31956

    Article  CAS  PubMed  Google Scholar 

  216. 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 114:777–789

    Article  CAS  PubMed  Google Scholar 

  217. Bai GR, Yang LH, Huang XY, Sun FZ (2006) Inositol 1,4,5-trisphosphate receptor type 1 phosphorylation and regulation by extracellular signal-regulated kinase. Biochem Biophys Res Commun 348:1319–1327

    Article  CAS  PubMed  Google Scholar 

  218. Beliveau E, Lessard V, Guillemette G (2014) STIM1 positively regulates the Ca2+ release activity of the inositol 1,4,5-trisphosphate receptor in bovine aortic endothelial cells. PLoS One 9:e114718

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  219. Haorah J, Knipe B, Gorantla S, Zheng J, Persidsky Y (2007) Alcohol-induced blood–brain barrier dysfunction is mediated via inositol 1,4,5-triphosphate receptor (IP3R)-gated intracellular calcium release. J Neurochem 100:324–336

    Article  CAS  PubMed  Google Scholar 

  220. Mountian I, Manolopoulos VG, De Smedt H, Parys JB, Missiaen L, Wuytack F (1999) Expression patterns of sarco/endoplasmic reticulum Ca(2+)-ATPase and inositol 1,4,5-trisphosphate receptor isoforms in vascular endothelial cells. Cell Calcium 25:371–380

    Article  CAS  PubMed  Google Scholar 

  221. Sundivakkam PC, Kwiatek AM, Sharma TT, Minshall RD, Malik AB, Tiruppathi C (2009) Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells. Am J Physiol Cell Physiol 296:C403–C413

    Article  CAS  PubMed  Google Scholar 

  222. Mountian I, Baba-Aïssa F, Jonas JC, Humbert de Smedt, Wuytack F, Parys JB (2001) Expression of Ca(2+) transport genes in platelets and endothelial cells in hypertension. Hypertension 37:135–141

    Article  CAS  PubMed  Google Scholar 

  223. Grayson TH, Haddock RE, Murray TP, Wojcikiewicz RJ, Hill CE (2004) Inositol 1,4,5-trisphosphate receptor subtypes are differentially distributed between smooth muscle and endothelial layers of rat arteries. Cell Calcium 36:447–458

    Article  CAS  PubMed  Google Scholar 

  224. Isakson BE (2008) Localized expression of an Ins(1,4,5)P3 receptor at the myoendothelial junction selectively regulates heterocellular Ca2+ communication. J Cell Sci 121:3664–3673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Beliveau E, Guillemette G (2009) Microfilament and microtubule assembly is required for the propagation of inositol trisphosphate receptor-induced Ca2+ waves in bovine aortic endothelial cells. J Cell Biochem 106:344–352

    Article  CAS  PubMed  Google Scholar 

  226. Laflamme K, Domingue O, Guillemette BI, Guillemette G (2002) Immunohistochemical localization of type 2 inositol 1,4,5-trisphosphate receptor to the nucleus of different mammalian cells. J Cell Biochem 85:219–228

    Article  CAS  PubMed  Google Scholar 

  227. Dragoni S, Laforenza U, Bonetti E, Lodola F, Bottino C, Berra-Romani R, Carlo Bongio G, Cinelli MP, Guerra G, Pedrazzoli P, Rosti V, Tanzi F, Moccia F (2011) Vascular endothelial growth factor stimulates endothelial colony forming cells proliferation and tubulogenesis by inducing oscillations in intracellular Ca2+ concentration. Stem Cells 29:1898–1907

    Article  CAS  PubMed  Google Scholar 

  228. Yuan Q, Yang J, Santulli G, Reiken SR, Wronska A, Kim MM, Osborne BW, Lacampagne A, Yin Y, Marks AR (2016) Maintenance of normal blood pressure is dependent on IP3R1-mediated regulation of eNOS. Proc Natl Acad Sci USA 113:8532–8537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Ledoux J, Taylor MS, Bonev AD, Hannah RM, Solodushko V, Shui B, Tallini Y, Kotlikoff MI, Nelson MT (2008) Functional architecture of inositol 1,4,5-trisphosphate signaling in restricted spaces of myoendothelial projections. Proc Natl Acad Sci USA 105:9627–9632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Toussaint F, Charbel C, Blanchette A, Ledoux J (2015) CaMKII regulates intracellular Ca(2)(+) dynamics in native endothelial cells. Cell Calcium 58:275–285

    Article  CAS  PubMed  Google Scholar 

  231. Raqeeb A, Sheng J, Ao N, Braun AP (2011) Purinergic P2Y2 receptors mediate rapid Ca(2+) mobilization, membrane hyperpolarization and nitric oxide production in human vascular endothelial cells. Cell Calcium 49:240–248

    Article  CAS  PubMed  Google Scholar 

  232. Wang S, Iring A, Strilic B, Albarran Juarez J, Kaur H, Troidl K, Tonack S, Burbiel JC, Muller CE, Fleming I, Lundberg JO, Wettschureck N, Offermanns S (2015) P2Y(2) and Gq/G(1)(1) control blood pressure by mediating endothelial mechanotransduction. J Clin Investig 125:3077–3086

    Article  PubMed  PubMed Central  Google Scholar 

  233. Gudi S, Nolan JP, Frangos JA (1998) Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition. Proc Natl Acad Sci USA 95:2515–2519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. de la Paz NG, Melchior B, Shayo FY, Frangos JA (2014) Heparan sulfates mediate the interaction between platelet endothelial cell adhesion molecule-1 (PECAM-1) and the Galphaq/11 subunits of heterotrimeric G proteins. J Biol Chem 289:7413–7424

    Article  CAS  Google Scholar 

  235. Marques FZ, Campain AE, Yang YH, Morris BJ (2010) Meta-analysis of genome-wide gene expression differences in onset and maintenance phases of genetic hypertension. Hypertension 56:319–324

    Article  CAS  PubMed  Google Scholar 

  236. Edwards JS, Atlas SR, Wilson SM, Cooper CF, Luo L, Stidley CA (2014) Integrated statistical and pathway approach to next-generation sequencing analysis: a family-based study of hypertension. BMC Proc 8:S104

    Article  PubMed  PubMed Central  Google Scholar 

  237. Aschner JL, Lennon JM, Fenton JW 2nd, Aschner M, Malik AB (1990) Enzymatic activity is necessary for thrombin-mediated increase in endothelial permeability. Am J Physiol 259:L270–L275

    CAS  PubMed  Google Scholar 

  238. Vu TK, Hung DT, Wheaton VI, Coughlin SR (1991) Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 64:1057–1068

    Article  CAS  PubMed  Google Scholar 

  239. Ash AS, Schild HO (1966) Receptors mediating some actions of histamine. Br J Pharmacol Chemother 27:427–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Hill SJ (1987) Histamine receptors branch out. Nature 327:104–105

    Article  CAS  PubMed  Google Scholar 

  241. Burgess GM, Godfrey PP, McKinney JS, Berridge MJ, Irvine RF, Putney JW Jr (1984) The second messenger linking receptor activation to internal Ca release in liver. Nature 309:63–66

    Article  CAS  PubMed  Google Scholar 

  242. Patel S, Joseph SK, Thomas AP (1999) Molecular properties of inositol 1,4,5-trisphosphate receptors. Cell Calcium 25:247–264

    Article  CAS  PubMed  Google Scholar 

  243. Putney JW Jr (1986) A model for receptor-regulated calcium entry. Cell Calcium 7:1–12

    Article  CAS  PubMed  Google Scholar 

  244. Putney JW Jr (1999) TRP, inositol 1,4,5-trisphosphate receptors, and capacitative calcium entry. Proc Natl Acad Sci USA 96:14669–14671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. 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 437:902–905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. 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 136:876–890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Bird GS, Hwang SY, Smyth JT, Fukushima M, Boyles RR, Putney JW Jr (2009) STIM1 is a calcium sensor specialized for digital signaling. Curr Biol 19:1724–1729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Zheng L, Stathopulos PB, Schindl R, Li GY, Romanin C, Ikura M (2011) Auto-inhibitory role of the EF-SAM domain of STIM proteins in store-operated calcium entry. Proc Natl Acad Sci USA 108:1337–1342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. 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 USA 104:9301–9306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. 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 et al (2008) Dynamic coupling of the putative coiled-coil domain of ORAI1 with STIM1 mediates ORAI1 channel activation. J Biol Chem 283:8014–8022

    Article  CAS  PubMed  Google Scholar 

  251. Alicia S, Angélica Z, Carlos S, Alfonso S, Vaca L (2008) STIM1 converts TRPC1 from a receptor-operated to a store-operated channel: moving TRPC1 in and out of lipid rafts. Cell Calcium 44:479–491

    Article  CAS  PubMed  Google Scholar 

  252. Cheng KT, Liu X, Ong HL, Ambudkar IS (2008) Functional requirement for Orai1 in store-operated TRPC1-STIM1 channels. J Biol Chem 283:12935–12940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  253. Kim MS, Zeng W, Yuan JP, Shin DM, Worley PF, Muallem S (2009) Native store-operated Ca2+ influx requires the channel function of Orai1 and TRPC1. J Biol Chem 284:9733–9741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Yeromin AV, Zhang SL, Jiang W, Yu Y, Safrina O, Cahalan MD (2006) Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature 443:226–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  255. 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 8:1003–1010

    Article  CAS  PubMed  Google Scholar 

  256. Savage SR, Bretz CA, Penn JS (2015) RNA-Seq reveals a role for NFAT-signaling in human retinal microvascular endothelial cells treated with TNFalpha. PLoS One 10:e0116941

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  257. Boulay G, Zhu X, Peyton M, Jiang M, Hurst R, Stefani E, Birnbaumer L (1997) Cloning and expression of a novel mammalian homolog of Drosophila transient receptor potential (Trp) involved in calcium entry secondary to activation of receptors coupled by the Gq class of G protein. J Biol Chem 272:29672–29680

    Article  CAS  PubMed  Google Scholar 

  258. Zitt C, Obukhov AG, Strubing C, Zobel A, Kalkbrenner F, Luckhoff A, Schultz G (1997) Expression of TRPC3 in Chinese hamster ovary cells results in calcium-activated cation currents not related to store depletion. J Cell Biol 138:1333–1341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  259. Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G (1999) Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397:259–263

    Article  CAS  PubMed  Google Scholar 

  260. Okada T, Inoue R, Yamazaki K, Maeda A, Kurosaki T, Yamakuni T, Tanaka I, Shimizu S, Ikenaka K, Imoto K, Mori Y (1999) Molecular and functional characterization of a novel mouse transient receptor potential protein homologue TRP7. Ca(2+)-permeable cation channel that is constitutively activated and enhanced by stimulation of G protein-coupled receptor. J Biol Chem 274:27359–27370

    Article  CAS  PubMed  Google Scholar 

  261. Weber EW, Han F, Tauseef M, Birnbaumer L, Mehta D, Muller WA (2015) TRPC6 is the endothelial calcium channel that regulates leukocyte transendothelial migration during the inflammatory response. J Exp Med 212:1883–1899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  262. Ross D, Joyner WL (1997) Resting distribution and stimulated translocation of protein kinase C isoforms alpha, epsilon and zeta in response to bradykinin and TNF in human endothelial cells. Endothelium 5:321–332

    Article  CAS  PubMed  Google Scholar 

  263. Hempel A, Maasch C, Heintze U, Lindschau C, Dietz R, Luft FC, Haller H (1997) High glucose concentrations increase endothelial cell permeability via activation of protein kinase C alpha. Circ Res 81:363–371

    Article  CAS  PubMed  Google Scholar 

  264. Ahmmed GU, Mehta D, Vogel S, Holinstat M, Paria BC, Tiruppathi C, Malik AB (2004) Protein kinase Calpha phosphorylates the TRPC1 channel and regulates store-operated Ca2+ entry in endothelial cells. J Biol Chem 279:20941–20949

    Article  CAS  PubMed  Google Scholar 

  265. Koya D, King GL (1998) Protein kinase C activation and the development of diabetic complications. Diabetes 47:859–866

    Article  CAS  PubMed  Google Scholar 

  266. Hui Y, Cheng Y, Smalera I, Jian W, Goldhahn L, Fitzgerald GA, Funk CD (2004) Directed vascular expression of human cysteinyl leukotriene 2 receptor modulates endothelial permeability and systemic blood pressure. Circulation 110:3360–3366

    Article  CAS  PubMed  Google Scholar 

  267. Moos MP, Mewburn JD, Kan FW, Ishii S, Abe M, Sakimura K, Noguchi K, Shimizu T, Funk CD (2008) Cysteinyl leukotriene 2 receptor-mediated vascular permeability via transendothelial vesicle transport. FASEB J 22:4352–4362

    Article  CAS  PubMed  Google Scholar 

  268. Ludtke SJ, Tran TP, Ngo QT, Moiseenkova-Bell VY, Chiu W, Serysheva II (2011) Flexible architecture of IP3R1 by Cryo-EM. Structure 19:1192–1199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  269. Bosanac I, Alattia JR, Mal TK, Chan J, Talarico S, Tong FK, Tong KI, Yoshikawa F, Furuichi T, Iwai M, Michikawa T, Mikoshiba K, Ikura M (2002) Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand. Nature 420:696–700

    Article  CAS  PubMed  Google Scholar 

  270. Bosanac I, Yamazaki H, Matsu-Ura T, Michikawa T, Mikoshiba K, Ikura M (2005) Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor. Mol Cell 17:193–203

    Article  CAS  PubMed  Google Scholar 

  271. Yamazaki H, Chan J, Ikura M, Michikawa T, Mikoshiba K (2010) Tyr-167/Trp-168 in type 1/3 inositol 1,4,5-trisphosphate receptor mediates functional coupling between ligand binding and channel opening. J Biol Chem 285:36081–36091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  272. Uchida K, Miyauchi H, Furuichi T, Michikawa T, Mikoshiba K (2003) Critical regions for activation gating of the inositol 1,4,5-trisphosphate receptor. J Biol Chem 278:16551–16560

    Article  CAS  PubMed  Google Scholar 

  273. Schug ZT, Joseph SK (2006) The role of the S4–S5 linker and C-terminal tail in inositol 1,4,5-trisphosphate receptor function. J Biol Chem 281:24431–24440

    Article  CAS  PubMed  Google Scholar 

  274. Boehning D, Joseph SK (2000) Direct association of ligand-binding and pore domains in homo- and heterotetrameric inositol 1,4,5-trisphosphate receptors. EMBO J 19:5450–5459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  275. Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280:69–77

    Article  CAS  PubMed  Google Scholar 

  276. Rose HJ, Dargan S, Shuai J, Parker I (2006) ‘Trigger’ events precede calcium puffs in Xenopus oocytes. Biophys J 91:4024–4032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  277. Parker I, Choi J, Yao Y (1996) Elementary events of InsP3-induced Ca2+ liberation in Xenopus oocytes: hot spots, puffs and blips. Cell Calcium 20:105–121

    Article  CAS  PubMed  Google Scholar 

  278. Huser J, Blatter LA (1997) Elementary events of agonist-induced Ca2+ release in vascular endothelial cells. Am J Physiol 273:C1775–C1782

    CAS  PubMed  Google Scholar 

  279. Burdyga T, Shmygol A, Eisner DA, Wray S (2003) A new technique for simultaneous and in situ measurements of Ca2+ signals in arteriolar smooth muscle and endothelial cells. Cell Calcium 34:27–33

    Article  CAS  PubMed  Google Scholar 

  280. Duza T, Sarelius IH (2004) Localized transient increases in endothelial cell Ca2+ in arterioles in situ: implications for coordination of vascular function. Am J Physiol Heart Circ Physiol 286:H2322–H2331

    Article  CAS  PubMed  Google Scholar 

  281. Kansui Y, Garland CJ, Dora KA (2008) Enhanced spontaneous Ca2+ events in endothelial cells reflect signalling through myoendothelial gap junctions in pressurized mesenteric arteries. Cell Calcium 44:135–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  282. Francis M, Waldrup JR, Qian X, Solodushko V, Meriwether J, Taylor MS (2016) Functional tuning of intrinsic endothelial Ca2+ dynamics in swine coronary arteries. Circ Res 118:1078–1090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  283. Wilson C, Saunter CD, Girkin JM, McCarron JG (2015) Pressure-dependent regulation of Ca2+ signalling in the vascular endothelium. J Physiol 593:5231–5253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  284. Diambra L, Marchant JS (2011) Inositol (1,4,5)-trisphosphate receptor microarchitecture shapes Ca2+ puff kinetics. Biophys J 100:822–831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  285. Bootman MD, Berridge MJ, Lipp P (1997) Cooking with calcium: the recipes for composing global signals from elementary events. Cell 91:367–373

    Article  CAS  PubMed  Google Scholar 

  286. Dargan SL, Parker I (2003) Buffer kinetics shape the spatiotemporal patterns of IP3-evoked Ca2+ signals. J Physiol 553:775–788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  287. Sun XP, Callamaras N, Marchant JS, Parker I (1998) A continuum of InsP3-mediated elementary Ca2+ signalling events in Xenopus oocytes. J Physiol 509(Pt 1):67–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  288. Smith IF, Parker I (2009) Imaging the quantal substructure of single IP3R channel activity during Ca2+ puffs in intact mammalian cells. Proc Natl Acad Sci USA 106:6404–6409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  289. Smith IF, Wiltgen SM, Parker I (2009) Localization of puff sites adjacent to the plasma membrane: functional and spatial characterization of Ca2+ signaling in SH-SY5Y cells utilizing membrane-permeant caged IP3. Cell Calcium 45:65–76

    Article  CAS  PubMed  Google Scholar 

  290. Marchant J, Callamaras N, Parker I (1999) Initiation of IP(3)-mediated Ca(2+) waves in Xenopus oocytes. EMBO J 18:5285–5299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  291. Falcke M (2003) On the role of stochastic channel behavior in intracellular Ca2+ dynamics. Biophys J 84:42–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  292. Skupin A, Kettenmann H, Winkler U, Wartenberg M, Sauer H, Tovey SC, Taylor CW, Falcke M (2008) How does intracellular Ca2+ oscillate: by chance or by the clock? Biophys J 94:2404–2411

    Article  CAS  PubMed  Google Scholar 

  293. Shuai J, Pearson JE, Foskett JK, Mak DO, Parker I (2007) A kinetic model of single and clustered IP3 receptors in the absence of Ca2+ feedback. Biophys J 93:1151–1162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  294. Ruckl M, Parker I, Marchant JS, Nagaiah C, Johenning FW, Rudiger S (2015) Modulation of elementary calcium release mediates a transition from puffs to waves in an IP3R cluster model. PLoS Comput Biol 11:e1003965

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  295. Gonzales AL, Yang Y, Sullivan MN, Sanders L, Dabertrand F, Hill-Eubanks DC, Nelson MT, Earley S (2014) A PLCgamma1-dependent, force-sensitive signaling network in the myogenic constriction of cerebral arteries. Sci Signal 7:ra49

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  296. Tai YT, Wu CC, Wu GJ, Chang HC, Chen TG, Chen RM, Chen TL (2000) Study of propofol in bovine aortic endothelium: I. Inhibitory effect on bradykinin-induced intracellular calcium immobilization. Acta Anaesthesiol Sin 38:181–186

    CAS  PubMed  Google Scholar 

  297. Cseresnyés Z, Schneider MF (2004) Peripheral hot spots for local Ca2+ release after single action potentials in sympathetic ganglion neurons. Biophys J 86:163–181

    Article  PubMed  PubMed Central  Google Scholar 

  298. Tasaka K, Mio M, Fujisawa K, Aoki I (1991) Role of microtubules on Ca2+ release from the endoplasmic reticulum and associated histamine release from rat peritoneal mast cells. Biochem Pharmacol 41:1031–1037

    Article  CAS  PubMed  Google Scholar 

  299. Isshiki M, Ando J, Korenaga R, Kogo H, Fujimoto T, Fujita T, Kamiya A (1998) Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich cell edges. Proc Natl Acad Sci USA 95:5009–5014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  300. Mitsuyama F, Sawai T (2001) The redistribution of Ca2+ stores with inositol 1,4,5-trisphosphate receptor to the cleavage furrow in a microtubule-dependent manner. Int J Dev Biol 45:861–868

    CAS  PubMed  Google Scholar 

  301. Vermassen E, Van Acker K, Annaert WG, Himpens B, Callewaert G, Missiaen L, De Smedt H, Parys JB (2003) Microtubule-dependent redistribution of the type-1 inositol 1,4,5-trisphosphate receptor in A7r5 smooth muscle cells. J Cell Sci 116:1269–1277

    Article  CAS  PubMed  Google Scholar 

  302. Aguilar-Maldonado B, Gomez-Viquez L, Garcia L, Del Angel RM, Arias-Montano JA, Guerrero-Hernandez A (2003) Histamine potentiates IP(3)-mediated Ca(2+) release via thapsigargin-sensitive Ca(2+) pumps. Cell Signal 15:689–697

    Article  CAS  PubMed  Google Scholar 

  303. Redondo PC, Harper AG, Sage SO, Rosado JA (2007) Dual role of tubulin-cytoskeleton in store-operated calcium entry in human platelets. Cell Signal 19:2147–2154

    Article  CAS  PubMed  Google Scholar 

  304. Takei K, Shin RM, Inoue T, Kato K, Mikoshiba K (1998) Regulation of nerve growth mediated by inositol 1,4,5-trisphosphate receptors in growth cones. Science 282:1705–1708

    Article  CAS  PubMed  Google Scholar 

  305. Zhang XF, Forscher P (2009) Rac1 modulates stimulus-evoked Ca(2+) release in neuronal growth cones via parallel effects on microtubule/endoplasmic reticulum dynamics and reactive oxygen species production. Mol Biol Cell 20:3700–3712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  306. Aihara Y, Inoue T, Tashiro T, Okamoto K, Komiya Y, Mikoshiba K (2001) Movement of endoplasmic reticulum in the living axon is distinct from other membranous vesicles in its rate, form, and sensitivity to microtubule inhibitors. J Neurosci Res 65:236–246

    Article  CAS  PubMed  Google Scholar 

  307. Ferreri-Jacobia M, Mak DO, Foskett JK (2005) Translational mobility of the type 3 inositol 1,4,5-trisphosphate receptor Ca2+ release channel in endoplasmic reticulum membrane. J Biol Chem 280:3824–3831

    Article  CAS  PubMed  Google Scholar 

  308. Graier WF, Paltauf-Doburzynska J, Hill BJ, Fleischhacker E, Hoebel BG, Kostner GM, Sturek M (1998) Submaximal stimulation of porcine endothelial cells causes focal Ca2+ elevation beneath the cell membrane. J Physiol 506(Pt 1):109–125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  309. Ribeiro CM, Reece J, Putney JW Jr (1997) Role of the cytoskeleton in calcium signaling in NIH 3T3 cells. An intact cytoskeleton is required for agonist-induced [Ca2+]i signaling, but not for capacitative calcium entry. J Biol Chem 272:26555–26561

    Article  CAS  PubMed  Google Scholar 

  310. Fogarty KE, Kidd JF, Turner A, Skepper JN, Carmichael J, Thorn P (2000) Microtubules regulate local Ca2+ spiking in secretory epithelial cells. J Biol Chem 275:22487–22494

    Article  CAS  PubMed  Google Scholar 

  311. Su LK, Qi Y (2001) Characterization of human MAPRE genes and their proteins. Genomics 71:142–149

    Article  CAS  PubMed  Google Scholar 

  312. Bieling P, Laan L, Schek H, Munteanu EL, Sandblad L, Dogterom M, Brunner D, Surrey T (2007) Reconstitution of a microtubule plus-end tracking system in vitro. Nature 450:1100–1105

    Article  CAS  PubMed  Google Scholar 

  313. Maurer SP, Bieling P, Cope J, Hoenger A, Surrey T (2011) GTPgammaS microtubules mimic the growing microtubule end structure recognized by end-binding proteins (EBs). Proc Natl Acad Sci USA 108:3988–3993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  314. Duellberg C, Cade NI, Holmes D, Surrey T (2016) The size of the EB cap determines instantaneous microtubule stability. Elife 5:e13470

    Article  PubMed  PubMed Central  Google Scholar 

  315. Komarova Y, Lansbergen G, Galjart N, Grosveld F, Borisy GG, Akhmanova A (2005) EB1 and EB3 control CLIP dissociation from the ends of growing microtubules. Mol Biol Cell 16:5334–5345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  316. Dixit R, Barnett B, Lazarus JE, Tokito M, Goldman YE, Holzbaur EL (2009) Microtubule plus-end tracking by CLIP-170 requires EB1. Proc Natl Acad Sci USA 106:492–497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  317. Honnappa S, Gouveia SM, Weisbrich A, Damberger FF, Bhavesh NS, Jawhari H, Grigoriev I, van Rijssel FJ, Buey RM, Lawera A, Jelesarov I, Winkler FK, Wuthrich K, Akhmanova A et al (2009) An EB1-binding motif acts as a microtubule tip localization signal. Cell 138:366–376

    Article  CAS  PubMed  Google Scholar 

  318. Slep KC, Rogers SL, Elliott SL, Ohkura H, Kolodziej PA, Vale RD (2005) Structural determinants for EB1-mediated recruitment of APC and spectraplakins to the microtubule plus end. J Cell Biol 168:587–598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  319. Hayashi I, Wilde A, Mal TK, Ikura M (2005) Structural basis for the activation of microtubule assembly by the EB1 and p150Glued complex. Mol Cell 19:449–460

    Article  CAS  PubMed  Google Scholar 

  320. Slep KC, Vale RD (2007) Structural basis of microtubule plus end tracking by XMAP215, CLIP-170, and EB1. Mol Cell 27:976–991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Pharmacology and The Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL, 60612, USA

    Mitchell Y. Sun, Melissa Geyer & Yulia A. Komarova

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  1. Mitchell Y. Sun
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  2. Melissa Geyer
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  3. Yulia A. Komarova
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Correspondence to Yulia A. Komarova.

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Supported by NIH Grants R01 HL103922 to Y.A.K; AHA AWARD 13PRE17090090 to M.G.

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The authors declare that they have no competing interests.

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Sun, M.Y., Geyer, M. & Komarova, Y.A. IP3 receptor signaling and endothelial barrier function. Cell. Mol. Life Sci. 74, 4189–4207 (2017). https://doi.org/10.1007/s00018-017-2624-8

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  • DOI: https://doi.org/10.1007/s00018-017-2624-8

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