Insights into the molecular mechanisms underlying mammalian P2X7 receptor functions and contributions in diseases, revealed by structural modeling and single nucleotide polymorphisms

Frontiers in Pharmacology

Volumn 4 MAY, Issue , 2013, Pages

  Jiang, Lin Hua ^a   Baldwin, Jocelyn M ^a   Roger, Sebastien ^b   Baldwin, Stephen A ^a  

^a UNIVERSITY OF LEEDS   (United Kingdom)

^b UNIVERSITÉ DE TOURS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; PURINERGIC P2X4 RECEPTOR; PURINERGIC P2X7 RECEPTOR;

BINDING SITE; CARBOXY TERMINAL SEQUENCE; DISEASES; GENETIC LINKAGE; HUMAN; ION TRANSPORT; MAMMAL; NONHUMAN; P2RX7 GENE; POINT MUTATION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN STRUCTURE; RECEPTOR BINDING; REVIEW; SEQUENCE HOMOLOGY; SINGLE NUCLEOTIDE POLYMORPHISM; SPECIES DIFFERENCE; ZEBRA FISH;

EID: 84881489108     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2013.00055     Document Type: Review

References (271)

1. Adinolfi, E., Callegari, M. G., Ferrari, D., Bolognesi, C., Minelli, M., Wieckowski, M. R., et al. (2005). Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth. Mol. Biol. Cell 16, 3260-3272.
2. Adinolfi, E., Cirillo, M., Woltersdorf, R., Falzoni, S., Chiozzi, P., Pellegatti, P., et al. (2010). Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor. FASEB J. 24, 3393-3404.
3. Adinolfi, E., Melchiorri, L., Falzoni, S., Chiozzi, P., Morelli, A., Tieghi, A., et al. (2002). P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia. Blood 99, 706-708.
4. Adinolfi, E., Raffaghello, L., Giuliani, A. L., Cavazzini, L., Capece, M., Chiozzi, P., et al. (2012). Expression of P2X7 receptor increases in vivo tumor growth. Cancer Res. 72, 2957-2969.
5. Adriouch, S., Bannas, P., Schwarz, N., Fliegert, R., Guse, A. H., Seman, M., et al. (2008). ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site. FASEB J. 22, 861-869.
6. Adriouch, S., Dox, C., Welge, V., Seman, M., Koch-Nolte, F., and Haag, F. (2002). Cutting edge: a natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor. J. Immunol. 169, 4108-4112
7. Adriouch, S., Scheuplein, F., Bahring, R., Seman, M., Boyer, O., Koch-Nolte, F., et al. (2009). Characterisation of the R276A gain-of-function mutation in the ectodomain of murine P2X7. Purinergic Signal. 5, 151-161.
8. Baconguis, I., and Gouaux, E. (2012). Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes. Nature 489, 400-405.
9. Barden, N., Harvey, M., Gagne, B., Shink, E., Tremblay, M., Raymond, C., et al. (2006). Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B, 374-382.
10. Baricordi, O. R., Melchiorri, L., Adinolfi, E., Falzoni, S., Chiozzi, P., Buell, G., et al. (1999). Increased proliferation rate of lymphoid cells transfected with the P2X(7) ATP receptor. J. Biol. Chem. 274, 33206-33208.
11. Baroja-Mazo, A., and Pelegrin, P. (2012). Modulating P2X7 receptor signaling during rheumatoid arthritis: new therapeutic approaches for bisphosphonates. J. Osteoporos. 2012, 408242.
12. Bean, B. P. (1990). ATP-activated channels in rat and bullfrog sensory neurons: concentration dependence and kinetics. J. Neurosci. 10, 1-10.
13. Bernier, L. P., Ase, A. R., Boue-Grabot, E., and Seguela, P. (2012). P2X4 receptor channels form large noncytolytic pores in resting and activated microglia. Glia 60, 728-737.
14. Boldt, W., Klapperstuck, M., Buttner, C., Sadtler, S., Schmalzing, G., and Markwardt, F. (2003). Glu496Ala polymorphism of human P2X7 receptor does not affect its electrophysiological phenotype. Am. J. Physiol. Cell Physiol. 284, C749-756.
15. Bradley, H. J., Baldwin, J. M., Goli, G. R., Johnson, B., Zou, J., Sivaprasadarao, A., et al. (2011a). Residues 155 and 348 contribute to the determination of P2X7 receptor function via distinct mechanisms revealed by single-nucleotide polymorphisms. J. Biol. Chem. 286, 8176-8187.
16. Bradley, H. J., Browne, L. E., Yang, W., and Jiang, L. H. (2011b). Pharmacological properties of the rhesus macaque monkey P2X7 receptor. Br. J. Pharmacol. 164, 743-754. Browne, L. E., Compan, V., Bragg, L., and North, R. A. (2013). P2X7 receptor channels allow direct permeation of nanometer-sized dyes. J. Neurosci. 33, 3557-3566.
17. Browne, L. E., Jiang, L. H., and North, R. A. (2010). New structure enlivens interest in P2X receptors. Trends Pharmacol. Sci. 31, 229-237.
18. Burnstock, G. (2012). Discovery of purinergic signalling, the initial resistance and current explosion of interest. Br. J. Pharmacol. 167, 238-255.
19. Burnstock, G., Fredholm, B. B., North, R. A., and Verkhratsky, A. (2010). The birth and postnatal development of purinergic signalling. Acta Physiol. (Oxf.) 199, 93-147.
20. Cabrini, G., Falzoni, S., Forchap, S. L., Pellegatti, P., Balboni, A., Agostini, P., et al. (2005). A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes. J. Immunol. 175, 82-89.
21. Cao, L., Broomhead, H. E., Young, M. T., and North, R. A. (2009). Polar residues in the second transmembrane domain of the rat P2X2 receptor that affect spontaneous gating, unitary conductance, and rectification. J. Neurosci. 29, 14257-14264.
22. Cao, L., Young, M. T., Broomhead, H. E., Fountain, S. J., and North, R. A. (2007). Thr339-to-serine substitution in rat P2X2 receptor second transmembrane domain causes constitutive opening and indicates a gating role for Lys308. J. Neurosci. 27, 12916-12923.
23. Chaumont, S., and Khakh, B. S. (2008). Patch-clamp coordinated spectroscopy shows P2X2 receptor permeability dynamics require cytosolic domain rearrangements but not Panx-1 channels. Proc. Natl. Acad. Sci. U.S.A. 105, 12063-12068.
24. Chessell, I. P., Michel, A. D., and Humphrey, P. P. (1997). Properties of the pore-forming P2X7 purinoceptor in mouse NTW8 microglial cells. Br. J. Pharmacol. 121, 1429-1437.
25. Chong, J. H., Zheng, G. G., Ma, Y. Y., Zhang, H. Y., Nie, K., Lin, Y. M., et al. (2010). The hyposensitive N187D P2X7 mutant promotes malignant progression in nude mice. J. Biol. Chem. 285, 36179-36187.
26. Cockcroft, S., and Gomperts, B. D. (1979). ATP induces nucleotide permeability in rat mast cells. Nature 279, 541-542.
27. Compan, V., Ulmann, L., Stelmashenko, O., Chemin, J., Chaumont, S., and Rassendren, F. (2012). P2X2 and P2X5 subunits define a new heteromeric receptor with P2X7-like properties. J. Neurosci. 32, 4284-4296.
28. Costa-Junior, H. M., Sarmento Vieira, F., and Coutinho-Silva, R. (2011). C terminus of the P2X7 receptor: treasure hunting. Purinergic Signal. 7, 7-19.
29. Dao-Ung, L. P., Fuller, S. J., Sluyter, R., Skarratt, K. K., Thunberg, U., Tobin, G., et al. (2004). Association of the 1513C polymorphism in the P2X7 gene with familial forms of chronic lymphocytic leukaemia. Br. J. Haematol. 125, 815-817.
30. Denlinger, L. C., Angelini, G., Schell, K., Green, D. N., Guadarrama, A. G., Prabhu, U., et al. (2005). Detection of human P2X7 nucleotide receptor polymorphisms by a novel monocyte pore assay predictive of alterations in lipopolysaccharide-induced cytokine production. J. Immunol. 174, 4424-4431.
31. Denlinger, L. C., Coursin, D. B., Schell, K., Angelini, G., Green, D. N., Guadarrama, A. G., et al. (2006). Human P2X7 pore function predicts allele linkage disequilibrium. Clin. Chem. 52, 995-1004.
32. Di Virgilio, F. (2012). Purines, purinergic receptors, and cancer. Cancer Res. 72, 5441-7544.
33. Ding, S., and Sachs, F. (1999). Single channel properties of P2X2 purinoceptors. J. Gen. Physiol. 113, 695-720.
34. Donnelly-Roberts, D. L., and Jarvis, M. F. (2007). Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states. Br. J. Pharmacol. 151, 571-579.
35. Eickhorst, A. N., Berson, A., Cockayne, D., Lester, H. A., and Khakh, B. S. (2002). Control of P2X(2) channel permeability by the cytosolic domain. J. Gen. Physiol. 120, 119-131.
36. Erhardt, A., Lucae, S., Unschuld, P. G., Ising, M., Kern, N., Salyakina, D., et al. (2007). Association of polymorphisms in P2RX7 and CaMKKb with anxiety disorders. J. Affect. Disord. 101, 159-168.
37. Evans, R. J. (2009). Orthosteric and allosteric binding sites of P2X receptors. Eur. Biophys. J. 38, 319-327.
38. Evans, R. J. (2010). Structural interpretation of P2X receptor mutagenesis studies on drug action. Br. J. Pharmacol. 161, 961-971.
39. Fonfria, E., Clay, W. C., Levy, D. S., Goodwin, J. A., Roman, S., Smith, G. D., et al. (2008). Cloning and pharmacological characterization of the guinea pig P2X7 receptor orthologue. Br. J. Pharmacol. 153, 544-556.
40. Franco-Martinez, S., Nino-Moreno, P., Bernal-Silva, S., Baranda, L., Rocha-Meza, M., Portales-Cervantes, L., et al. (2006). Expression and function of the purinergic receptor P2X7 in patients with pulmonary tuberculosis. Clin. Exp. Immunol. 146, 253-261.
41. Gartland, A., Skarratt, K. K., Hocking, L. J., Parsons, C., Stokes, L., Jørgensen, N. R., et al. (2012). Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women. Eur. J. Hum. Genet. 20, 559-564.
42. Gidlof, O., Smith, J. G., Melander, O., Lovkvist, H., Hedblad, B., Engstrom, G., et al. (2012). A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events. PLoS ONE 7:e37491. doi:10.1371/journal.pone.0037491
43. Gonzales, E. B., Kawate, T., and Gouaux, E. (2009). Pore architecture and ion sites in acid-sensing ion channels and P2X receptors. Nature 460, 599-604.
44. Gordon, J. L. (1986). Extracellular ATP: effects, sources and fate. Biochem. J. 233, 309-319.
45. Green, E. K., Grozeva, D., Raybould, R., Elvidge, G., Macgregor, S., Craig, I., et al. (2009). P2RX7: a bipolar and unipolar disorder candidate susceptibility gene? Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 1063-1069.
46. Grigoroiu-Serbanescu, M., Herms, S., Muhleisen, T. W., Georgi, A., Diaconu, C. C., Strohmaier, J., et al. (2009). Variation in P2RX7 candidate gene (rs2230912) is not associated with bipolar I disorder and unipolar major depression in four European samples. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 1017-1021.
47. Gu, B. J., Sluyter, R., Skarratt, K. K., Shemon, A. N., Dao-Ung, L. P., Fuller, S. J., et al. (2004). An Arg307 to Gln polymorphism within the ATP-binding site causes loss of function of the human P2X7 receptor. J. Biol. Chem. 279, 31287-31295.
48. Gu, B. J., Zhang, W., Worthington, R. A., Sluyter, R., Dao-Ung, P., Petrou, S., et al. (2001). A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor. J. Biol. Chem. 276, 11135-11142.
49. Guile, S. D., Alcaraz, L., Birkinshaw, T. N., Bowers, K. C., Ebden, M. R., Furber, M., et al. (2009). Antagonists of the P2X(7) receptor. From lead identification to drug development. J. Med. Chem. 52, 3123-3141.
50. Gulbransen, B. D., Bashashati, M., Hirota, S. A., Gui, X., Roberts, J. A., Macdonald, J. A., et al. (2012). Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis. Nat. Med. 18, 600-604.
51. Gum, R. J., Wakefield, B., and Jarvis, M. F. (2012). P2X receptor antagonists for pain management: examination of binding and physicochemical properties. Purinergic Signal. 8, 41-56.
52. Hattori, M., and Gouaux, E. (2012). Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature 485, 207-212.
53. Hejjas, K., Szekely, A., Domotor, E., Halmai, Z., Balogh, G., Schilling, B., et al. (2009). Association between depression and the Gln460Arg polymorphism of P2RX7 gene: a dimensional approach. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 295-299.
54. Hong, S., Schwarz, N., Brass, A., Seman, M., Haag, F., Koch-Nolte, F., et al. (2009). Differential regulation of P2X7 receptor activation by extracellular nicotinamide adenine dinucleotide and ecto-ADP-ribosyltransferases in murine macrophages and T cells. J. Immunol. 183, 578-592.
55. Husted, L. B., Harsløf, T., Stenkjær, L., Carstens, M., Jørgensen, N. R., and Langdahl, B. L. (2013). Functional polymorphisms in the P2X7 receptor gene are associated with osteoporosis. Osteoporos. Int. 24, 949-959.
56. Jelassi, B., Anchelin, M., Chamouton, J., Cayuela, M.L., Clarysse, L., Li, J., et al. (2013). Anthraquinone emodin inhibits human cancer cell invasiveness by antagonizing P2X7 receptors. Carcinogenesis. doi:10.1093/carcin/bgt099. [Epub ahead of print].
57. Jiang, L. H. (2009). Inhibition of P2X(7) receptors by divalent cations: old action and new insight. Eur. Biophys. J. 38, 339-346.
58. Jiang, L. H. (2012). P2X receptor-mediated ATP purinergic signalling in health and disease. Cell Health Cytoskelet. 4, 83-101.
59. Jiang, L. H., Kim, M., Spelta, V., Bo, X., Surprenant, A., and North, R. A. (2003). Subunit arrangement in P2X receptors. J. Neurosci. 23, 8903-8910
60. Jiang, L. H., Rassendren, F., Mackenzie, A., Zhang, Y. H., Surprenant, A., and North, R. A. (2005). N-methyl-D-glucamine and propidium dyes utilize different permeation pathways at rat P2X(7) receptors. Am. J. Physiol. Cell Physiol. 289, C1295-C1302.
61. Jiang, L. H., Rassendren, F., Surprenant, A., and North, R. A. (2000). Identification of amino acid residues contributing to the ATP-binding site of a purinergic P2X receptor. J. Biol. Chem. 275, 34190-34196.
62. Jiang, R., Lemoine, D., Martz, A., Taly, A., Gonin, S., Prado De Carvalho, L., et al. (2011). Agonist trapped in ATP-binding sites of the P2X2 receptor. Proc. Natl. Acad. Sci. U.S.A. 108, 9066-9071.
63. Jiang, R., Taly, A., and Grutter, T. (2013). Moving through the gate in ATP-activated P2X receptors. Trends Biochem. Sci. 38, 20-29.
64. Jiang, R., Taly, A., Lemoine, D., Martz, A., Cunrath, O., and Grutter, T. (2012). Tightening of the ATP-binding sites induces the opening of P2X receptor channels. EMBO J. 31, 2134-2143.
65. Jørgensen, N. R., Husted, L. B., Skarratt, K. K., Stokes, L., Tofteng, C. L., Kvist, T., et al. (2012). Single-nucleotide polymorphisms in the P2X7 receptor gene are associated with post-menopausal bone loss and vertebral fractures. Eur. J. Hum. Genet. 20, 675-681.
66. Kaczmarek-Hajek, K., Lorinczi, E., Hausmann, R., and Nicke, A. (2012). Molecular and functional properties of P2X receptors - recent progress and persisting challenges. Purinergic Signal. 8, 375-417.
67. Kawate, T., Michel, J. C., Birdsong, W. T., and Gouaux, E. (2009). Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature 460, 592-598.
68. Kawate, T., Robertson, J. L., Li, M., Silberberg, S. D., and Swartz, K. J. (2011). Ion access pathway to the transmembrane pore in P2X receptor channels. J. Gen. Physiol. 137, 579-590.
69. Ke, H. Z., Qi, H., Weidema, A. F., Zhang, Q., Panupinthu, N., Crawford, D. T., et al. (2003). Deletion of the P2X7 nucleotide receptor reveals its regulatory roles in bone formation and resorption. Mol. Endocrinol. 17, 1356-1367.
70. Keystone, E. C., Wang, M. M., Layton, M., Hollis, S., McInnes, I. B., and Team, D. C. S. (2012). Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine. Ann. Rheum. Dis. 71, 1630-1635.
71. Khakh, B. S., Bao, X. R., Labarca, C., and Lester, H. A. (1999). Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds. Nat. Neurosci. 2, 322-330.
72. Khakh, B. S., and North, R. A. (2006). P2X receptors as cell-surface ATP sensors in health and disease. Nature 442, 527-532.
73. Khakh, B. S., and North, R. A. (2012). Neuromodulation by extracellular ATP and P2X receptors in the CNS. Neuron 76, 51-69.
74. Kucenas, S., Li, Z., Cox, J. A., Egan, T. M., and Voigt, M. M. (2003). Molecular characterization of the zebrafish P2X receptor subunit gene family. Neuroscience 121, 935-945.
75. Le Stunff, H., Auger, R., Kanellopoulos, J., and Raymond, M. N. (2004). The Pro-451 to Leu polymorphism within the C-terminal tail of P2X7 receptor impairs cell death but not phospholipase D activation in murine thymocytes. J. Biol. Chem. 279, 16918-16926.
76. Li, M., Kawate, T., Silberberg, S. D., and Swartz, K. J. (2010). Pore-opening mechanism in trimeric P2X receptor channels. Nat. Commun. 1, 44.
77. Liu, L., Zou, J., Liu, X., Jiang, L. H., and Li, J. (2010). Inhibition of ATP-induced macrophage death by emodin via antagonizing P2X7 receptor. Eur. J. Pharmacol. 640, 15-19.
78. Liu, X., Surprenant, A., Mao, H. J., Roger, S., Xia, R., Bradley, H., et al. (2008). Identification of key residues coordinating functional inhibition of P2X7 receptors by zinc and copper. Mol. Pharmacol. 73, 252-259.
79. Lucae, S., Salyakina, D., Barden, N., Harvey, M., Gagne, B., Labbe, M., et al. (2006). P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder. Hum. Mol. Genet. 15, 2438-2445.
80. Marques-da-Silva, C., Chaves, M. M., Castro, N. G., Coutinho-Silva, R., and Guimaraes, M. Z. (2011). Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 receptor-expressing cells: implications for its therapeutic action. Br. J. Pharmacol. 163, 912-926.
81. Marquez-Klaka, B., Rettinger, J., Bhargava, Y., Eisele, T., and Nicke, A. (2007). Identification of an intersubunit cross-link between substituted cysteine residues located in the putative ATP binding site of the P2X1 receptor. J. Neurosci. 27, 1456-1466.
82. Marquez-Klaka, B., Rettinger, J., and Nicke, A. (2009). Inter-subunit disulfide cross-linking in homomeric and heteromeric P2X receptors. Eur. Biophys. J. 38, 329-338.
83. McQuillin, A., Bass, N. J., Choudhury, K., Puri, V., Kosmin, M., Lawrence, J., et al. (2009). Case-control studies show that a non-conservative amino-acid change from a glutamine to arginine in the P2RX7 purinergic receptor protein is associated with both bipolar- and unipolar-affective disorders. Mol. Psychiatry 14, 614-620.
84. Michel, A. D., Clay, W. C., Ng, S. W., Roman, S., Thompson, K., Condreay, J. P., et al. (2008). Identification of regions of the P2X(7) receptor that contribute to human and rat species differences in antagonist effects. Br. J. Pharmacol. 155, 738-751.
85. Monif, M., Reid, C. A., Powell, K. L., Smart, M. L., and Williams, D. A. (2009). The P2X7 receptor drives microglial activation and proliferation: a trophic role for P2X7R pore. J. Neurosci. 29, 3781-3791.
86. Nicke, A., Kuan, Y. H., Masin, M., Rettinger, J., Marquez-Klaka, B., Bender, O., et al. (2009). A functional P2X7 splice variant with an alternative transmembrane domain 1 escapes gene inactivation in P2X7 knock-out mice. J. Biol. Chem. 284, 25813-25822.
87. Nino-Moreno, P., Portales-Perez, D., Hernandez-Castro, B., Portales-Cervantes, L., Flores-Meraz, V., Baranda, L., et al. (2007). P2X7 and NRAMP1/SLC11 A1 gene polymorphisms in Mexican mestizo patients with pulmonary tuberculosis. Clin. Exp. Immunol. 148, 469-477.
88. North, R. A. (2002). Molecular physiology of P2X receptors. Physiol. Rev. 82, 1013-1067.
89. North, R. A., and Surprenant, A. (2000). Pharmacology of cloned P2X receptors. Annu. Rev. Pharmacol. Toxicol. 40, 563-580.
90. Nückel, H., Frey, U. H., Dürig, J., Dührsen, U., and Siffert, W. (2004). 1513A/C polymorphism in the P2X7 receptor gene in chronic lymphocytic leukemia: absence of correlation with clinical outcome. Eur. J. Haematol. 72, 259-263.
91. Ohlendorff, S. D., Tofteng, C. L., Jensen, J. E., Petersen, S., Civitelli, R., Fenger, M., et al. (2007). Single nucleotide polymorphisms in the P2X7 gene are associated to fracture risk and to effect of estrogen treatment. Pharmacogenet. Genomics 177, 555-567.
92. Oyanguren-Desez, O., Rodriguez-Antiguedad, A., Villoslada, P., Domercq, M., Alberdi, E., and Matute, C. (2011). Gain-of-function of P2X7 receptor gene variants in multiple sclerosis. Cell Calcium 50, 468-472.
93. Paukert, M., Hidayat, S., and Grunder, S. (2002). The P2X(7) receptor from Xenopus laevis: formation of a large pore in Xenopus oocytes. FEBS Lett. 513, 253-258.
94. Pelegrin, P. (2011). Many ways to dilate the P2X7 receptor pore. Br. J. Pharmacol. 163, 908-911.
95. Pelegrin, P., and Surprenant, A. (2006). Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J. 25, 5071-5082.
96. Portales-Cervantes, L., Nino-Moreno, P., Salgado-Bustamante, M., Garcia-Hernandez, M. H., Baranda-Candido, L., Reynaga-Hernandez, E., et al. (2012). The His155Tyr (489C>T) single nucleotide polymorphism of P2RX7 gene confers an enhanced function of P2X7 receptor in immune cells from patients with rheumatoid arthritis. Cell. Immunol. 276, 168-175.
97. Qu, Y., Misaghi, S., Newton, K., Gilmour, L. L., Louie, S., Cupp, J. E., et al. (2011). Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J. Immunol. 186, 6553-6561.
98. Rassendren, F., Buell, G., Newbolt, A., North, R. A., and Surprenant, A. (1997a). Identification of amino acid residues contributing to the pore of a P2X receptor. EMBO J. 16, 3446-3454.
99. Rassendren, F., Buell, G. N., Virginio, C., Collo, G., North, R. A., and Surprenant, A. (1997b). The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA. J. Biol. Chem. 272, 5482-5486.
100. Riteau, N., Gasse, P., Fauconnier, L., Gombault, A., Couegnat, M., Fick, L., et al. (2010). Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am. J. Respir. Crit. Care Med. 182, 774-783.
101. Roberts, J. A., Allsopp, R. C., El Ajouz, S., Vial, C., Schmid, R., Young, M. T., et al. (2012). Agonist binding evokes extensive conformational changes in the extracellular domain of the ATP-gated human P2X1 receptor ion channel. Proc. Natl. Acad. Sci. U.S.A. 109, 4663-4667.
102. Roger, S., Gillet, L., Baroja-Mazo, A., Surprenant, A., and Pelegrin, P. (2010a). C-terminal calmodulin-binding motif differentially controls human and rat P2X7 receptor current facilitation. J. Biol. Chem. 285, 17514-17524.
103. Roger, S., Mei, Z. Z., Baldwin, J. M., Dong, L., Bradley, H., Baldwin, S. A., et al. (2010b). Single nucleotide polymorphisms that were identified in affective mood disorders affect ATP-activated P2X7 receptor functions. J. Psychiatr. Res. 44, 347-355.
104. Roger, S., and Pelegrin, P. (2011). P2X7 receptor antagonism in the treatment of cancers. Expert Opin. Investig. Drugs 20, 875-880.
105. Roger, S., Pelegrin, P., and Surprenant, A. (2008). Facilitation of P2X7 receptor currents and membrane blebbing via constitutive and dynamic calmodulin binding. J. Neurosci. 28, 6393-6401.
106. Roman, S., Cusdin, F. S., Fonfria, E., Goodwin, J. A., Reeves, J., Lappin, S. C., et al. (2009). Cloning and pharmacological characterization of the dog P2X7 receptor. Br. J. Pharmacol. 158, 1513-1526.
107. Samways, D. S., Khakh, B. S., Dutertre, S., and Egan, T. M. (2011). Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors). Proc. Natl. Acad. Sci. U.S.A. 108, 13800-13805.
108. Schwarz, N., Drouot, L., Nicke, A., Fliegert, R., Boyer, O., Guse, A. H., et al. (2012). Alternative splicing of the N-terminal cytosolic and transmembrane domains of P2X7 controls gating of the ion channel by ADP-ribosylation. PLoS ONE 7:e41269. doi:10.1371/journal.pone.0041269
109. Schwarz, N., Fliegert, R., Adriouch, S., Seman, M., Guse, A. H., Haag, F., et al. (2009). Activation of the P2X7 ion channel by soluble and covalently bound ligands. Purinergic Signal. 5, 139-149.
110. Seman, M., Adriouch, S., Scheuplein, F., Krebs, C., Freese, D., Glowacki, G., et al. (2003). NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor. Immunity 19, 571-582.
111. Shemon, A. N., Sluyter, R., Fernando, S. L., Clarke, A. L., Dao-Ung, L. P., Skarratt, K. K., et al. (2006). A Thr357 to Ser polymorphism in homozygous and compound heterozygous subjects causes absent or reduced P2X7 function and impairs ATP-induced mycobacterial killing by macrophages. J. Biol. Chem. 281, 2079-2086.
112. Sluyter, R., Shemon, A. N., and Wiley, J. S. (2004). Glu496 to Ala polymorphism in the P2X7 receptor impairs ATP-induced IL-1 beta release from human monocytes. J. Immunol. 172, 3399-3405.
113. Sorge, R. E., Trang, T., Dorfman, R., Smith, S. B., Beggs, S., Ritchie, J., et al. (2012). Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nat. Med. 18, 595-599.
114. Starczynski, J., Pepper, C., Pratt, G., Hooper, L., Thomas, A., Hoy, T., et al. (2003). The P2X7 receptor gene polymorphism 1513 A- -->C has no effect on clinical prognostic markers, in vitro sensitivity to fludarabine, Bcl-2 family protein expression or survival in B-cell chronic lymphocytic leukaemia. Br. J. Haematol. 123, 66-71.
115. Stelmashenko, O., Lalo, U., Yang, Y., Bragg, L., North, R. A., and Compan, V. (2012). Activation of trimeric P2X2 receptors by fewer than three ATP molecules. Mol. Pharmacol. 82, 760-766.
116. Stock, T. C., Bloom, B. J., Wei, N., Ishaq, S., Park, W., Wang, X., et al. (2012). Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate. J. Rheumatol. 39, 720-727.
117. Stokes, L., Fuller, S. J., Sluyter, R., Skarratt, K. K., Gu, B. J., and Wiley, J. S. (2010). Two haplotypes of the P2X(7) receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1beta secretion. FASEB J. 24, 2916-2927.
118. Suadicani, S. O., Iglesias, R., Wang, J., Dahl, G., Spray, D. C., and Scemes, E. (2012). ATP signaling is deficient in cultured pannexin1-null mouse astrocytes. Glia 60, 1106-1116.
119. Sun, C., Chu, J., Singh, S., and Salter, R. D. (2010). Identification and characterization of a novel variant of the human P2X(7) receptor resulting in gain of function. Purinergic Signal. 6, 31-45.
120. Surprenant, A., and North, R. A. (2009). Signaling at purinergic P2X receptors. Annu. Rev. Physiol. 71, 333-359.
121. Surprenant, A., Rassendren, F., Kawashima, E., North, R. A., and Buell, G. (1996). The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272, 735-738.
122. Syberg, S., Schwarz, P., Petersen, S., Steinberg, T. H., Jensen, J. E., Teilmann, J., et al. (2012). Association between P2X7 receptor polymorphisms and bone status in mice. J. Osteoporos. 2012, 637986.
123. Thunberg, U., Tobin, G., Johnson, A., Soderberg, O., Padyukov, L., Hultdin, M., et al. (2002). Polymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia. Lancet 360, 1935-1939.
124. Virginio, C., Mackenzie, A., North, R. A., and Surprenant, A. (1999a). Kinetics of cell lysis, dye uptake and permeability changes in cells expressing the rat P2X7 receptor. J. Physiol. (Lond.) 519(Pt 2), 335-346
125. Virginio, C., Mackenzie, A., Rassendren, F. A., North, R. A., and Surprenant, A. (1999b). Pore dilation of neuronal P2X receptor channels. Nat. Neurosci. 2, 315-321.
126. Wesselius, A., Bours, M. J., Henriksen, Z., Syberg, S., Petersen, S., Schwarz, P., et al. (2013). Association of P2X7 receptor polymorphisms with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients. Osteoporos. Int. 24, 1235-1246.
127. Wiley, J. S., Dao-Ung, L. P., Gu, B. J., Sluyter, R., Shemon, A. N., Li, C., et al. (2002). A loss-of-function polymorphic mutation in the cytolytic P2X7 receptor gene and chronic lymphocytic leukaemia: a molecular study. Lancet 359, 1114-1119.
128. Wiley, J. S., Dao-Ung, L. P., Li, C., Shemon, A. N., Gu, B. J., Smart, M. L., et al. (2003). An Ile-568 to Asn polymorphism prevents normal trafficking and function of the human P2X7 receptor. J. Biol. Chem. 278, 17108-17113.
129. Wilkinson, W. J., Jiang, L. H., Surprenant, A., and North, R. A. (2006). Role of ectodomain lysines in the subunits of the heteromeric P2X2/3 receptor. Mol. Pharmacol. 70, 1159-1163.
130. Worthington, R. A., Smart, M. L., Gu, B. J., Williams, D. A., Petrou, S., Wiley, J. S., et al. (2002). Point mutations confer loss of ATP-induced human P2X(7) receptor function. FEBS Lett. 512, 43-46.
131. Xu, X. J., Boumechache, M., Robinson, L. E., Marschall, V., Gorecki, D. C., Masin, M., et al. (2012). Splice variants of the P2X7 receptor reveal differential agonist dependence and functional coupling with pannexin-1. J. Cell Sci. 125, 3776-3789.
132. Yan, Z., Khadra, A., Li, S., Tomic, M., Sherman, A., and Stojilkovic, S. S. (2010). Experimental characterization and mathematical modeling of P2X7 receptor channel gating. J. Neurosci. 30, 14213-14224.
133. Young, M. T. (2010). P2X receptors: dawn of the post-structure era. Trends Biochem. Sci. 35, 83-90.
134. Young, M. T., Pelegrin, P., and Surprenant, A. (2006). Identification of Thr283 as a key determinant of P2X7 receptor function. Br. J. Pharmacol. 149, 261-268.
135. Young, M. T., Pelegrin, P., and Surprenant, A. (2007). Amino acid residues in the P2X7 receptor that mediate differential sensitivity to ATP and BzATP. Mol. Pharmacol. 71, 92-100.
136. Zhang, L. Y., Ibbotson, R. E., Orchard, J. A., Gardiner, A. C., Seear, R. V., Chase, A. J., et al. (2003). P2X7 polymorphism and chronic lymphocytic leukaemia: lack of correlation with incidence, survival and abnormalities of chromosome 12. Leukemia 17, 2097-2100. References Adinolfi, E., Callegari, M. G., Ferrari, D., Bolognesi, C., Minelli, M., Wieckowski, M. R., et al. (2005). Basal activation of the P2X7 ATP receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth. Mol. Biol. Cell 16, 3260-3272.
137. Adinolfi, E., Cirillo, M., Woltersdorf, R., Falzoni, S., Chiozzi, P., Pellegatti, P., et al. (2010). Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor. FASEB J. 24, 3393-3404.
138. Adinolfi, E., Melchiorri, L., Falzoni, S., Chiozzi, P., Morelli, A., Tieghi, A., et al. (2002). P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia. Blood 99, 706-708.
139. Adinolfi, E., Raffaghello, L., Giuliani, A. L., Cavazzini, L., Capece, M., Chiozzi, P., et al. (2012). Expression of P2X7 receptor increases in vivo tumor growth. Cancer Res. 72, 2957-2969.
140. Adriouch, S., Bannas, P., Schwarz, N., Fliegert, R., Guse, A. H., Seman, M., et al. (2008). ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site. FASEB J. 22, 861-869.
141. Adriouch, S., Dox, C., Welge, V., Seman, M., Koch-Nolte, F., and Haag, F. (2002). Cutting edge: a natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor. J. Immunol. 169, 4108-4112.
142. Adriouch, S., Scheuplein, F., Bahring, R., Seman, M., Boyer, O., Koch-Nolte, F., et al. (2009). Characterisation of the R276A gain-of-function mutation in the ectodomain of murine P2X7. Purinergic Signal. 5, 151-161.
143. Baconguis, I., and Gouaux, E. (2012). Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes. Nature 489, 400-405.
144. Barden, N., Harvey, M., Gagne, B., Shink, E., Tremblay, M., Raymond, C., et al. (2006). Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B, 374-382.
145. Baricordi, O. R., Melchiorri, L., Adinolfi, E., Falzoni, S., Chiozzi, P., Buell, G., et al. (1999). Increased proliferation rate of lymphoid cells transfected with the P2X(7) ATP receptor. J. Biol. Chem. 274, 33206-33208.
146. Baroja-Mazo, A., and Pelegrin, P. (2012). Modulating P2X7 receptor signaling during rheumatoid arthritis: new therapeutic approaches for bisphosphonates. J. Osteoporos. 2012, 408242.
147. Bean, B. P. (1990). ATP-activated channels in rat and bullfrog sensory neurons: concentration dependence and kinetics. J. Neurosci. 10, 1-10.
148. Bernier, L. P., Ase, A. R., Boue-Grabot, E., and Seguela, P. (2012). P2X4 receptor channels form large noncytolytic pores in resting and activated microglia. Glia 60, 728-737.
149. Boldt, W., Klapperstuck, M., Buttner, C., Sadtler, S., Schmalzing, G., and Markwardt, F. (2003). Glu496Ala polymorphism of human P2X7 receptor does not affect its electrophysiological phenotype. Am. J. Physiol. Cell Physiol. 284, C749-756.
150. Bradley, H. J., Baldwin, J. M., Goli, G. R., Johnson, B., Zou, J., Sivaprasadarao, A., et al. (2011a). Residues 155 and 348 contribute to the determination of P2X7 receptor function via distinct mechanisms revealed by single-nucleotide polymorphisms. J. Biol. Chem. 286, 8176-8187.
151. Bradley, H. J., Browne, L. E., Yang, W., and Jiang, L. H. (2011b). Pharmacological properties of the rhesus macaque monkey P2X7 receptor. Br. J. Pharmacol. 164, 743-754. Browne, L. E., Compan, V., Bragg, L., and North, R. A. (2013). P2X7 receptor channels allow direct permeation of nanometer-sized dyes. J. Neurosci. 33, 3557-3566.
152. Browne, L. E., Jiang, L. H., and North, R. A. (2010). New structure enlivens interest in P2X receptors. Trends Pharmacol. Sci. 31, 229-237.
153. Burnstock, G. (2012). Discovery of purinergic signalling, the initial resistance and current explosion of interest. Br. J. Pharmacol. 167, 238-255.
154. Burnstock, G., Fredholm, B. B., North, R. A., and Verkhratsky, A. (2010). The birth and postnatal development of purinergic signalling. Acta Physiol. (Oxf.) 199, 93-147.
155. Cabrini, G., Falzoni, S., Forchap, S. L., Pellegatti, P., Balboni, A., Agostini, P., et al. (2005). A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes. J. Immunol. 175, 82-89.
156. Cao, L., Broomhead, H. E., Young, M. T., and North, R. A. (2009). Polar residues in the second transmembrane domain of the rat P2X2 receptor that affect spontaneous gating, unitary conductance, and rectification. J. Neurosci. 29, 14257-14264.
157. Cao, L., Young, M. T., Broomhead, H. E., Fountain, S. J., and North, R. A. (2007). Thr339-to-serine substitution in rat P2X2 receptor second transmembrane domain causes constitutive opening and indicates a gating role for Lys308. J. Neurosci. 27, 12916-12923.
158. Chaumont, S., and Khakh, B. S. (2008). Patch-clamp coordinated spectroscopy shows P2X2 receptor permeability dynamics require cytosolic domain rearrangements but not Panx-1 channels. Proc. Natl. Acad. Sci. U.S.A. 105, 12063-12068.
159. Chessell, I. P., Michel, A. D., and Humphrey, P. P. (1997). Properties of the pore-forming P2X7 purinoceptor in mouse NTW8 microglial cells. Br. J. Pharmacol. 121, 1429-1437.
160. Chong, J. H., Zheng, G. G., Ma, Y. Y., Zhang, H. Y., Nie, K., Lin, Y. M., et al. (2010). The hyposensitive N187D P2X7 mutant promotes malignant progression in nude mice. J. Biol. Chem. 285, 36179-36187.
161. Cockcroft, S., and Gomperts, B. D. (1979). ATP induces nucleotide permeability in rat mast cells. Nature 279, 541-542.
162. Compan, V., Ulmann, L., Stelmashenko, O., Chemin, J., Chaumont, S., and Rassendren, F. (2012). P2X2 and P2X5 subunits define a new heteromeric receptor with P2X7-like properties. J. Neurosci. 32, 4284-4296.
163. Costa-Junior, H. M., Sarmento Vieira, F., and Coutinho-Silva, R. (2011). C terminus of the P2X7 receptor: treasure hunting. Purinergic Signal. 7, 7-19.
164. Dao-Ung, L. P., Fuller, S. J., Sluyter, R., Skarratt, K. K., Thunberg, U., Tobin, G., et al. (2004). Association of the 1513C polymorphism in the P2X7 gene with familial forms of chronic lymphocytic leukaemia. Br. J. Haematol. 125, 815-817.
165. Denlinger, L. C., Angelini, G., Schell, K., Green, D. N., Guadarrama, A. G., Prabhu, U., et al. (2005). Detection of human P2X7 nucleotide receptor polymorphisms by a novel monocyte pore assay predictive of alterations in lipopolysaccharide-induced cytokine production. J. Immunol. 174, 4424-4431.
166. Denlinger, L. C., Coursin, D. B., Schell, K., Angelini, G., Green, D. N., Guadarrama, A. G., et al. (2006). Human P2X7 pore function predicts allele linkage disequilibrium. Clin. Chem. 52, 995-1004.
167. Di Virgilio, F. (2012). Purines, purinergic receptors, and cancer. Cancer Res. 72, 5441-7544.
168. Ding, S., and Sachs, F. (1999). Single channel properties of P2X2 purinoceptors. J. Gen. Physiol. 113, 695-720.
169. Donnelly-Roberts, D. L., and Jarvis, M. F. (2007). Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states. Br. J. Pharmacol. 151, 571-579.
170. Eickhorst, A. N., Berson, A., Cockayne, D., Lester, H. A., and Khakh, B. S. (2002). Control of P2X(2) channel permeability by the cytosolic domain. J. Gen. Physiol. 120, 119-131.
171. Erhardt, A., Lucae, S., Unschuld, P. G., Ising, M., Kern, N., Salyakina, D., et al. (2007). Association of polymorphisms in P2RX7 and CaMKKb with anxiety disorders. J. Affect. Disord. 101, 159-168.
172. Evans, R. J. (2009). Orthosteric and allosteric binding sites of P2X receptors. Eur. Biophys. J. 38, 319-327.
173. Evans, R. J. (2010). Structural interpretation of P2X receptor mutagenesis studies on drug action. Br. J. Pharmacol. 161, 961-971.
174. Fonfria, E., Clay, W. C., Levy, D. S., Goodwin, J. A., Roman, S., Smith, G. D., et al. (2008). Cloning and pharmacological characterization of the guinea pig P2X7 receptor orthologue. Br. J. Pharmacol. 153, 544-556.
175. Franco-Martinez, S., Nino-Moreno, P., Bernal-Silva, S., Baranda, L., Rocha-Meza, M., Portales-Cervantes, L., et al. (2006). Expression and function of the purinergic receptor P2X7 in patients with pulmonary tuberculosis. Clin. Exp. Immunol. 146, 253-261.
176. Gartland, A., Skarratt, K. K., Hocking, L. J., Parsons, C., Stokes, L., Jørgensen, N. R., et al. (2012). Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women. Eur. J. Hum. Genet. 20, 559-564.
177. Gidlof, O., Smith, J. G., Melander, O., Lovkvist, H., Hedblad, B., Engstrom, G., et al. (2012). A common missense variant in the ATP receptor P2X7 is associated with reduced risk of cardiovascular events. PLoS ONE 7:e37491. doi:10.1371/journal.pone.0037491
178. Gonzales, E. B., Kawate, T., and Gouaux, E. (2009). Pore architecture and ion sites in acid-sensing ion channels and P2X receptors. Nature 460, 599-604.
179. Gordon, J. L. (1986). Extracellular ATP: effects, sources and fate. Biochem. J. 233, 309-319.
180. Green, E. K., Grozeva, D., Raybould, R., Elvidge, G., Macgregor, S., Craig, I., et al. (2009). P2RX7: a bipolar and unipolar disorder candidate susceptibility gene? Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 1063-1069.
181. Grigoroiu-Serbanescu, M., Herms, S., Muhleisen, T. W., Georgi, A., Diaconu, C. C., Strohmaier, J., et al. (2009). Variation in P2RX7 candidate gene (rs2230912) is not associated with bipolar I disorder and unipolar major depression in four European samples. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 1017-1021.
182. Gu, B. J., Sluyter, R., Skarratt, K. K., Shemon, A. N., Dao-Ung, L. P., Fuller, S. J., et al. (2004). An Arg307 to Gln polymorphism within the ATP-binding site causes loss of function of the human P2X7 receptor. J. Biol. Chem. 279, 31287-31295.
183. Gu, B. J., Zhang, W., Worthington, R. A., Sluyter, R., Dao-Ung, P., Petrou, S., et al. (2001). A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor. J. Biol. Chem. 276, 11135-11142.
184. Guile, S. D., Alcaraz, L., Birkinshaw, T. N., Bowers, K. C., Ebden, M. R., Furber, M., et al. (2009). Antagonists of the P2X(7) receptor. From lead identification to drug development. J. Med. Chem. 52, 3123-3141.
185. Gulbransen, B. D., Bashashati, M., Hirota, S. A., Gui, X., Roberts, J. A., Macdonald, J. A., et al. (2012). Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis. Nat. Med. 18, 600-604.
186. Gum, R. J., Wakefield, B., and Jarvis, M. F. (2012). P2X receptor antagonists for pain management: examination of binding and physicochemical properties. Purinergic Signal. 8, 41-56.
187. Hattori, M., and Gouaux, E. (2012). Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature 485, 207-212.
188. Hejjas, K., Szekely, A., Domotor, E., Halmai, Z., Balogh, G., Schilling, B., et al. (2009). Association between depression and the Gln460Arg polymorphism of P2RX7 gene: a dimensional approach. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 295-299.
189. Hong, S., Schwarz, N., Brass, A., Seman, M., Haag, F., Koch-Nolte, F., et al. (2009). Differential regulation of P2X7 receptor activation by extracellular nicotinamide adenine dinucleotide and ecto-ADP-ribosyltransferases in murine macrophages and T cells. J. Immunol. 183, 578-592.
190. Husted, L. B., Harsløf, T., Stenkjær, L., Carstens, M., Jørgensen, N. R., and Langdahl, B. L. (2013). Functional polymorphisms in the P2X7 receptor gene are associated with osteoporosis. Osteoporos. Int. 24, 949-959.
191. Jelassi, B., Anchelin, M., Chamouton, J., Cayuela, M.L., Clarysse, L., Li, J., et al. (2013). Anthraquinone emodin inhibits human cancer cell invasiveness by antagonizing P2X7 receptors. Carcinogenesis. doi:10.1093/carcin/bgt099. [Epub ahead of print].
192. Jiang, L. H. (2009). Inhibition of P2X(7) receptors by divalent cations: old action and new insight. Eur. Biophys. J. 38, 339-346.
193. Jiang, L. H. (2012). P2X receptor-mediated ATP purinergic signalling in health and disease. Cell Health Cytoskelet. 4, 83-101.
194. Jiang, L. H., Kim, M., Spelta, V., Bo, X., Surprenant, A., and North, R. A. (2003). Subunit arrangement in P2X receptors. J. Neurosci. 23, 8903-8910
195. Jiang, L. H., Rassendren, F., Mackenzie, A., Zhang, Y. H., Surprenant, A., and North, R. A. (2005). N-methyl-D-glucamine and propidium dyes utilize different permeation pathways at rat P2X(7) receptors. Am. J. Physiol. Cell Physiol. 289, C1295-C1302.
196. Jiang, L. H., Rassendren, F., Surprenant, A., and North, R. A. (2000). Identification of amino acid residues contributing to the ATP-binding site of a purinergic P2X receptor. J. Biol. Chem. 275, 34190-34196.
197. Jiang, R., Lemoine, D., Martz, A., Taly, A., Gonin, S., Prado De Carvalho, L., et al. (2011). Agonist trapped in ATP-binding sites of the P2X2 receptor. Proc. Natl. Acad. Sci. U.S.A. 108, 9066-9071.
198. Jiang, R., Taly, A., and Grutter, T. (2013). Moving through the gate in ATP-activated P2X receptors. Trends Biochem. Sci. 38, 20-29.
199. Jiang, R., Taly, A., Lemoine, D., Martz, A., Cunrath, O., and Grutter, T. (2012). Tightening of the ATP-binding sites induces the opening of P2X receptor channels. EMBO J. 31, 2134-2143.
200. Jørgensen, N. R., Husted, L. B., Skarratt, K. K., Stokes, L., Tofteng, C. L., Kvist, T., et al. (2012). Single-nucleotide polymorphisms in the P2X7 receptor gene are associated with post-menopausal bone loss and vertebral fractures. Eur. J. Hum. Genet. 20, 675-681.
201. Kaczmarek-Hajek, K., Lorinczi, E., Hausmann, R., and Nicke, A. (2012). Molecular and functional properties of P2X receptors - recent progress and persisting challenges. Purinergic Signal. 8, 375-417.
202. Kawate, T., Michel, J. C., Birdsong, W. T., and Gouaux, E. (2009). Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature 460, 592-598.
203. Kawate, T., Robertson, J. L., Li, M., Silberberg, S. D., and Swartz, K. J. (2011). Ion access pathway to the transmembrane pore in P2X receptor channels. J. Gen. Physiol. 137, 579-590.
204. Ke, H. Z., Qi, H., Weidema, A. F., Zhang, Q., Panupinthu, N., Crawford, D. T., et al. (2003). Deletion of the P2X7 nucleotide receptor reveals its regulatory roles in bone formation and resorption. Mol. Endocrinol. 17, 1356-1367.
205. Keystone, E. C., Wang, M. M., Layton, M., Hollis, S., McInnes, I. B., and Team, D. C. S. (2012). Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine. Ann. Rheum. Dis. 71, 1630-1635.
206. Khakh, B. S., Bao, X. R., Labarca, C., and Lester, H. A. (1999). Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds. Nat. Neurosci. 2, 322-330.
207. Khakh, B. S., and North, R. A. (2006). P2X receptors as cell-surface ATP sensors in health and disease. Nature 442, 527-532.
208. Khakh, B. S., and North, R. A. (2012). Neuromodulation by extracellular ATP and P2X receptors in the CNS. Neuron 76, 51-69.
209. Kucenas, S., Li, Z., Cox, J. A., Egan, T. M., and Voigt, M. M. (2003). Molecular characterization of the zebrafish P2X receptor subunit gene family. Neuroscience 121, 935-945.
210. Le Stunff, H., Auger, R., Kanellopoulos, J., and Raymond, M. N. (2004). The Pro-451 to Leu polymorphism within the C-terminal tail of P2X7 receptor impairs cell death but not phospholipase D activation in murine thymocytes. J. Biol. Chem. 279, 16918-16926.
211. Li, M., Kawate, T., Silberberg, S. D., and Swartz, K. J. (2010). Pore-opening mechanism in trimeric P2X receptor channels. Nat. Commun. 1, 44.
212. Liu, L., Zou, J., Liu, X., Jiang, L. H., and Li, J. (2010). Inhibition of ATP-induced macrophage death by emodin via antagonizing P2X7 receptor. Eur. J. Pharmacol. 640, 15-19.
213. Liu, X., Surprenant, A., Mao, H. J., Roger, S., Xia, R., Bradley, H., et al. (2008). Identification of key residues coordinating functional inhibition of P2X7 receptors by zinc and copper. Mol. Pharmacol. 73, 252-259.
214. Lucae, S., Salyakina, D., Barden, N., Harvey, M., Gagne, B., Labbe, M., et al. (2006). P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder. Hum. Mol. Genet. 15, 2438-2445.
215. Marques-da-Silva, C., Chaves, M. M., Castro, N. G., Coutinho-Silva, R., and Guimaraes, M. Z. (2011). Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 receptor-expressing cells: implications for its therapeutic action. Br. J. Pharmacol. 163, 912-926.
216. Marquez-Klaka, B., Rettinger, J., Bhargava, Y., Eisele, T., and Nicke, A. (2007). Identification of an intersubunit cross-link between substituted cysteine residues located in the putative ATP binding site of the P2X1 receptor. J. Neurosci. 27, 1456-1466.
217. Marquez-Klaka, B., Rettinger, J., and Nicke, A. (2009). Inter-subunit disulfide cross-linking in homomeric and heteromeric P2X receptors. Eur. Biophys. J. 38, 329-338.
218. McQuillin, A., Bass, N. J., Choudhury, K., Puri, V., Kosmin, M., Lawrence, J., et al. (2009). Case-control studies show that a non-conservative amino-acid change from a glutamine to arginine in the P2RX7 purinergic receptor protein is associated with both bipolar- and unipolar-affective disorders. Mol. Psychiatry 14, 614-620.
219. Michel, A. D., Clay, W. C., Ng, S. W., Roman, S., Thompson, K., Condreay, J. P., et al. (2008). Identification of regions of the P2X(7) receptor that contribute to human and rat species differences in antagonist effects. Br. J. Pharmacol. 155, 738-751.
220. Monif, M., Reid, C. A., Powell, K. L., Smart, M. L., and Williams, D. A. (2009). The P2X7 receptor drives microglial activation and proliferation: a trophic role for P2X7R pore. J. Neurosci. 29, 3781-3791.
221. Nicke, A., Kuan, Y. H., Masin, M., Rettinger, J., Marquez-Klaka, B., Bender, O., et al. (2009). A functional P2X7 splice variant with an alternative transmembrane domain 1 escapes gene inactivation in P2X7 knock-out mice. J. Biol. Chem. 284, 25813-25822.
222. Nino-Moreno, P., Portales-Perez, D., Hernandez-Castro, B., Portales-Cervantes, L., Flores-Meraz, V., Baranda, L., et al. (2007). P2X7 and NRAMP1/SLC11 A1 gene polymorphisms in Mexican mestizo patients with pulmonary tuberculosis. Clin. Exp. Immunol. 148, 469-477.
223. North, R. A. (2002). Molecular physiology of P2X receptors. Physiol. Rev. 82, 1013-1067.
224. North, R. A., and Surprenant, A. (2000). Pharmacology of cloned P2X receptors. Annu. Rev. Pharmacol. Toxicol. 40, 563-580.
225. Nückel, H., Frey, U. H., Dürig, J., Dührsen, U., and Siffert, W. (2004). 1513A/C polymorphism in the P2X7 receptor gene in chronic lymphocytic leukemia: absence of correlation with clinical outcome. Eur. J. Haematol. 72, 259-263.
226. Ohlendorff, S. D., Tofteng, C. L., Jensen, J. E., Petersen, S., Civitelli, R., Fenger, M., et al. (2007). Single nucleotide polymorphisms in the P2X7 gene are associated to fracture risk and to effect of estrogen treatment. Pharmacogenet. Genomics 177, 555-567.
227. Oyanguren-Desez, O., Rodriguez-Antiguedad, A., Villoslada, P., Domercq, M., Alberdi, E., and Matute, C. (2011). Gain-of-function of P2X7 receptor gene variants in multiple sclerosis. Cell Calcium 50, 468-472.
228. Paukert, M., Hidayat, S., and Grunder, S. (2002). The P2X(7) receptor from Xenopus laevis: formation of a large pore in Xenopus oocytes. FEBS Lett. 513, 253-258.
229. Pelegrin, P. (2011). Many ways to dilate the P2X7 receptor pore. Br. J. Pharmacol. 163, 908-911.
230. Pelegrin, P., and Surprenant, A. (2006). Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J. 25, 5071-5082.
231. Portales-Cervantes, L., Nino-Moreno, P., Salgado-Bustamante, M., Garcia-Hernandez, M. H., Baranda-Candido, L., Reynaga-Hernandez, E., et al. (2012). The His155Tyr (489C>T) single nucleotide polymorphism of P2RX7 gene confers an enhanced function of P2X7 receptor in immune cells from patients with rheumatoid arthritis. Cell. Immunol. 276, 168-175.
232. Qu, Y., Misaghi, S., Newton, K., Gilmour, L. L., Louie, S., Cupp, J. E., et al. (2011). Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J. Immunol. 186, 6553-6561.
233. Rassendren, F., Buell, G., Newbolt, A., North, R. A., and Surprenant, A. (1997a). Identification of amino acid residues contributing to the pore of a P2X receptor. EMBO J. 16, 3446-3454.
234. Rassendren, F., Buell, G. N., Virginio, C., Collo, G., North, R. A., and Surprenant, A. (1997b). The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA. J. Biol. Chem. 272, 5482-5486.
235. Riteau, N., Gasse, P., Fauconnier, L., Gombault, A., Couegnat, M., Fick, L., et al. (2010). Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am. J. Respir. Crit. Care Med. 182, 774-783.
236. Roberts, J. A., Allsopp, R. C., El Ajouz, S., Vial, C., Schmid, R., Young, M. T., et al. (2012). Agonist binding evokes extensive conformational changes in the extracellular domain of the ATP-gated human P2X1 receptor ion channel. Proc. Natl. Acad. Sci. U.S.A. 109, 4663-4667.
237. Roger, S., Gillet, L., Baroja-Mazo, A., Surprenant, A., and Pelegrin, P. (2010a). C-terminal calmodulin-binding motif differentially controls human and rat P2X7 receptor current facilitation. J. Biol. Chem. 285, 17514-17524.
238. Roger, S., Mei, Z. Z., Baldwin, J. M., Dong, L., Bradley, H., Baldwin, S. A., et al. (2010b). Single nucleotide polymorphisms that were identified in affective mood disorders affect ATP-activated P2X7 receptor functions. J. Psychiatr. Res. 44, 347-355.
239. Roger, S., and Pelegrin, P. (2011). P2X7 receptor antagonism in the treatment of cancers. Expert Opin. Investig. Drugs 20, 875-880.
240. Roger, S., Pelegrin, P., and Surprenant, A. (2008). Facilitation of P2X7 receptor currents and membrane blebbing via constitutive and dynamic calmodulin binding. J. Neurosci. 28, 6393-6401.
241. Roman, S., Cusdin, F. S., Fonfria, E., Goodwin, J. A., Reeves, J., Lappin, S. C., et al. (2009). Cloning and pharmacological characterization of the dog P2X7 receptor. Br. J. Pharmacol. 158, 1513-1526.
242. Samways, D. S., Khakh, B. S., Dutertre, S., and Egan, T. M. (2011). Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors). Proc. Natl. Acad. Sci. U.S.A. 108, 13800-13805.
243. Schwarz, N., Drouot, L., Nicke, A., Fliegert, R., Boyer, O., Guse, A. H., et al. (2012). Alternative splicing of the N-terminal cytosolic and transmembrane domains of P2X7 controls gating of the ion channel by ADP-ribosylation. PLoS ONE 7:e41269. doi:10.1371/journal.pone.0041269
244. Schwarz, N., Fliegert, R., Adriouch, S., Seman, M., Guse, A. H., Haag, F., et al. (2009). Activation of the P2X7 ion channel by soluble and covalently bound ligands. Purinergic Signal. 5, 139-149.
245. Seman, M., Adriouch, S., Scheuplein, F., Krebs, C., Freese, D., Glowacki, G., et al. (2003). NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor. Immunity 19, 571-582.
246. Shemon, A. N., Sluyter, R., Fernando, S. L., Clarke, A. L., Dao-Ung, L. P., Skarratt, K. K., et al. (2006). A Thr357 to Ser polymorphism in homozygous and compound heterozygous subjects causes absent or reduced P2X7 function and impairs ATP-induced mycobacterial killing by macrophages. J. Biol. Chem. 281, 2079-2086.
247. Sluyter, R., Shemon, A. N., and Wiley, J. S. (2004). Glu496 to Ala polymorphism in the P2X7 receptor impairs ATP-induced IL-1 beta release from human monocytes. J. Immunol. 172, 3399-3405.
248. Sorge, R. E., Trang, T., Dorfman, R., Smith, S. B., Beggs, S., Ritchie, J., et al. (2012). Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nat. Med. 18, 595-599.
249. Starczynski, J., Pepper, C., Pratt, G., Hooper, L., Thomas, A., Hoy, T., et al. (2003). The P2X7 receptor gene polymorphism 1513 A- -->C has no effect on clinical prognostic markers, in vitro sensitivity to fludarabine, Bcl-2 family protein expression or survival in B-cell chronic lymphocytic leukaemia. Br. J. Haematol. 123, 66-71.
250. Stelmashenko, O., Lalo, U., Yang, Y., Bragg, L., North, R. A., and Compan, V. (2012). Activation of trimeric P2X2 receptors by fewer than three ATP molecules. Mol. Pharmacol. 82, 760-766.
251. Stock, T. C., Bloom, B. J., Wei, N., Ishaq, S., Park, W., Wang, X., et al. (2012). Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate. J. Rheumatol. 39, 720-727.
252. Stokes, L., Fuller, S. J., Sluyter, R., Skarratt, K. K., Gu, B. J., and Wiley, J. S. (2010). Two haplotypes of the P2X(7) receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1beta secretion. FASEB J. 24, 2916-2927.
253. Suadicani, S. O., Iglesias, R., Wang, J., Dahl, G., Spray, D. C., and Scemes, E. (2012). ATP signaling is deficient in cultured pannexin1-null mouse astrocytes. Glia 60, 1106-1116.
254. Sun, C., Chu, J., Singh, S., and Salter, R. D. (2010). Identification and characterization of a novel variant of the human P2X(7) receptor resulting in gain of function. Purinergic Signal. 6, 31-45.
255. Surprenant, A., and North, R. A. (2009). Signaling at purinergic P2X receptors. Annu. Rev. Physiol. 71, 333-359.
256. Surprenant, A., Rassendren, F., Kawashima, E., North, R. A., and Buell, G. (1996). The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272, 735-738.
257. Syberg, S., Schwarz, P., Petersen, S., Steinberg, T. H., Jensen, J. E., Teilmann, J., et al. (2012). Association between P2X7 receptor polymorphisms and bone status in mice. J. Osteoporos. 2012, 637986.
258. Thunberg, U., Tobin, G., Johnson, A., Soderberg, O., Padyukov, L., Hultdin, M., et al. (2002). Polymorphism in the P2X7 receptor gene and survival in chronic lymphocytic leukaemia. Lancet 360, 1935-1939.
259. Virginio, C., Mackenzie, A., North, R. A., and Surprenant, A. (1999a). Kinetics of cell lysis, dye uptake and permeability changes in cells expressing the rat P2X7 receptor. J. Physiol. (Lond.) 519(Pt 2), 335-346.
260. Virginio, C., Mackenzie, A., Rassendren, F. A., North, R. A., and Surprenant, A. (1999b). Pore dilation of neuronal P2X receptor channels. Nat. Neurosci. 2, 315-321.
261. Wesselius, A., Bours, M. J., Henriksen, Z., Syberg, S., Petersen, S., Schwarz, P., et al. (2013). Association of P2X7 receptor polymorphisms with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients. Osteoporos. Int. 24, 1235-1246.
262. Wiley, J. S., Dao-Ung, L. P., Gu, B. J., Sluyter, R., Shemon, A. N., Li, C., et al. (2002). A loss-of-function polymorphic mutation in the cytolytic P2X7 receptor gene and chronic lymphocytic leukaemia: a molecular study. Lancet 359, 1114-1119.
263. Wiley, J. S., Dao-Ung, L. P., Li, C., Shemon, A. N., Gu, B. J., Smart, M. L., et al. (2003). An Ile-568 to Asn polymorphism prevents normal trafficking and function of the human P2X7 receptor. J. Biol. Chem. 278, 17108-17113.
264. Wilkinson, W. J., Jiang, L. H., Surprenant, A., and North, R. A. (2006). Role of ectodomain lysines in the subunits of the heteromeric P2X2/3 receptor. Mol. Pharmacol. 70, 1159-1163.
265. Worthington, R. A., Smart, M. L., Gu, B. J., Williams, D. A., Petrou, S., Wiley, J. S., et al. (2002). Point mutations confer loss of ATP-induced human P2X(7) receptor function. FEBS Lett. 512, 43-46.
266. Xu, X. J., Boumechache, M., Robinson, L. E., Marschall, V., Gorecki, D. C., Masin, M., et al. (2012). Splice variants of the P2X7 receptor reveal differential agonist dependence and functional coupling with pannexin-1. J. Cell Sci. 125, 3776-3789.
267. Yan, Z., Khadra, A., Li, S., Tomic, M., Sherman, A., and Stojilkovic, S. S. (2010). Experimental characterization and mathematical modeling of P2X7 receptor channel gating. J. Neurosci. 30, 14213-14224.
268. Young, M. T. (2010). P2X receptors: dawn of the post-structure era. Trends Biochem. Sci. 35, 83-90.
269. Young, M. T., Pelegrin, P., and Surprenant, A. (2006). Identification of Thr283 as a key determinant of P2X7 receptor function. Br. J. Pharmacol. 149, 261-268.
270. Young, M. T., Pelegrin, P., and Surprenant, A. (2007). Amino acid residues in the P2X7 receptor that mediate differential sensitivity to ATP and BzATP. Mol. Pharmacol. 71, 92-100.
271. Zhang, L. Y., Ibbotson, R. E., Orchard, J. A., Gardiner, A. C., Seear, R. V., Chase, A. J., et al. (2003). P2X7 polymorphism and chronic lymphocytic leukaemia: lack of correlation with incidence, survival and abnormalities of chromosome 12. Leukemia 17, 2097-2100.