Rare platelet GPCR variants: What can we learn?

British Journal of Pharmacology

Volumn 172, Issue 13, 2015, Pages 3242-3253

  Nisar, S P ^a   Jones, M L ^a   Cunningham, M R ^a   Mumford, A D ^a   Mundell, Stuart J ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; PURINERGIC P2Y12 RECEPTOR; THROMBOXANE A2 RECEPTOR; ANTITHROMBOCYTIC AGENT;

BLEEDING; FUNCTIONAL GENOMICS; GENETIC ASSOCIATION; GENETIC VARIABILITY; HETEROZYGOSITY; HOMOZYGOSITY; HUMAN; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; REVIEW; STRUCTURE ACTIVITY RELATION; THROMBOCYTE ACTIVATION; DRUG EFFECTS; GENETIC VARIATION; GENETICS; METABOLISM; THROMBOCYTE;

BLOOD PLATELETS; GENETIC VARIATION; HUMANS; PLATELET AGGREGATION INHIBITORS; RECEPTORS, G-PROTEIN-COUPLED;

EID: 84937500791     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12941     Document Type: Review

References (82)

1. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013a). The Concise Guide to PHARMACOLOGY 2013/14: G Protein-Coupled Receptors. Br J Pharmacol 170: 1459-1581.
2. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013b). The Concise Guide to PHARMACOLOGY 2013/14: Catalytic Receptors. Br J Pharmacol 170: 1676-1705.
3. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013c). The Concise Guide to PHARMACOLOGY 2013/14: Enzymes. Br J Pharmacol 170: 1797-1867.
4. Cambria-Kiely JA, Gandhi PJ, (2002). Aspirin resistance and genetic polymorphisms. J Thromb Thrombolysis 14: 51-58.
5. Capodanno D, Bhatt DL, Goto S, O'Donoghue ML, Moliterno DJ, Tamburino C, et al. (2012). Safety and efficacy of protease-activated receptor-1 antagonists in patients with coronary artery disease: a meta-analysis of randomized clinical trials. J Thromb Haemost 10: 2006-2015.
6. Capra V, Veltri A, Foglia C, Crimaldi L, Habib A, Parenti M, et al. (2004). Mutational analysis of the highly conserved ERY motif of the thromboxane A2 receptor: alternative role in G protein-coupled receptor signaling. Mol Pharmacol 66: 880-889.
7. Cattaneo M, (2011a). Bleeding manifestations of congenital and drug-induced defects of the platelet P2Y12 receptor for adenosine diphosphate. Thromb Haemost 105 (Suppl. 1): S67-S74.
8. Cattaneo M, (2011b). The clinical relevance of response variability to antiplatelet therapy. Hematology Am Soc Hematol Educ Program 2011: 70-75.
9. Cattaneo M, (2011c). The platelet P2Y(1)(2) receptor for adenosine diphosphate: congenital and drug-induced defects. Blood 117: 2102-2112.
10. Cattaneo M, Zighetti ML, Lombardi R, Martinez C, Lecchi A, Conley PB, et al. (2003). Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding. Proc Natl Acad Sci U S A 100: 1978-1983.
11. Chakraborty R, Pydi SP, Gleim S, Bhullar RP, Hwa J, Dakshinamurti S, et al. (2013). New insights into structural determinants for prostanoid thromboxane A2 receptor- and prostacyclin receptor-G protein coupling. Mol Cell Biol 33: 184-193.
12. Chen H, Dong X, Zhou M, Shi H, Luo X, (2011). Docking-based virtual screening of potential human P2Y12 receptor antagonists. Acta Biochim Biophys Sin (Shanghai) 43: 400-408.
13. Costanzi S, Mamedova L, Gao ZG, Jacobson KA, (2004). Architecture of P2Y nucleotide receptors: structural comparison based on sequence analysis, mutagenesis, and homology modeling. J Med Chem 47: 5393-5404.
14. Cox D, Smith R, Quinn M, Theroux P, Crean P, Fitzgerald DJ, (2000). Evidence of platelet activation during treatment with a GPIIb/IIIa antagonist in patients presenting with acute coronary syndromes. J Am Coll Cardiol 36: 1514-1519.
15. Cunningham MR, McIntosh KA, Pediani JD, Robben J, Cooke AE, Nilsson M, et al. (2012). Novel role for proteinase-activated receptor 2 (PAR2) in membrane trafficking of proteinase-activated receptor 4 (PAR4). J Biol Chem 287: 16656-16669.
16. Cunningham MR, Nisar SP, Cooke AE, Emery ED, Mundell SJ, (2013). Differential endosomal sorting of a novel P2Y(12) purinoreceptor mutant. Traffic 14: 585-598.
17. Daly ME, Dawood BB, Lester WA, Peake IR, Rodeghiero F, Goodeve AC, et al. (2009). Identification and characterization of a novel P2Y 12 variant in a patient diagnosed with type 1 von Willebrand disease in the European MCMDM-1VWD study. Blood 113: 4110-4113.
18. Dawood BB, Lowe GC, Lordkipanidze M, Bem D, Daly ME, Makris M, et al. (2012). Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel. Blood 120: 5041-5049.
19. Deckert J, Nothen MM, Rietschel M, Wildenauer D, Bondy B, Ertl MA, et al. (1996). Human adenosine A2a receptor (A2aAR) gene: systematic mutation screening in patients with schizophrenia. J Neural Transm 103: 1447-1455.
20. Dupont A, Fontana P, Bachelot-Loza C, Reny JL, Bieche I, Desvard F, et al. (2003). An intronic polymorphism in the PAR-1 gene is associated with platelet receptor density and the response to SFLLRN. Blood 101: 1833-1840.
21. Fanelli F, Mauri M, Capra V, Raimondi F, Guzzi F, Ambrosio M, et al. (2011). Light on the structure of thromboxane A(2) receptor heterodimers. Cell and Mol Life Sci 68: 3109-3120.
22. Feher G, Feher A, Pusch G, Lupkovics G, Szapary L, Papp E, (2009). The genetics of antiplatelet drug resistance. Clin Genet 75: 1-18.
23. Fontana G, Ware J, Cattaneo M, (2009). Haploinsufficiency of the platelet P2Y12 gene in a family with congenital bleeding diathesis. Haematologica 94: 581-584.
24. Fuse I, Hattori A, Mito M, Higuchi W, Yahata K, Shibata A, et al. (1996). Pathogenetic analysis of five cases with a platelet disorder characterized by the absence of thromboxane A2 (TXA2)-induced platelet aggregation in spite of normal TXA2 binding activity. Thromb Haemost 76: 1080-1085.
25. Giusti B, Gori AM, Marcucci R, Saracini C, Sestini I, Paniccia R, et al. (2007). Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10 + 12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual antiplatelet treatment in high-risk vascular patients. Pharmacogenet Genomics 17: 1057-1064.
26. Glanzmann E, (1918). Hereditare hamorrhagische thrombasthenie: ein beitrag zur pathologie der blut plattchen. J Kinderkr 88: 113-141.
27. Goodeve A, Eikenboom J, Castaman G, Rodeghiero F, Federici AB, Batlle J, et al. (2007). Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD). Blood 109: 112-121.
28. Higuchi W, Fuse I, Hattori A, Aizawa Y, (1999). Mutations of the platelet thromboxane A2 (TXA2) receptor in patients characterized by the absence of TXA2-induced platelet aggregation despite normal TXA2 binding activity. Thromb Haemost 82: 1528-1531.
29. Hirata T, Kakizuka A, Ushikubi F, Fuse I, Okuma M, Narumiya S, (1994). Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder. J Clin Invest 94: 1662-1667.
30. Hoffmann K, Sixel U, Di Pasquale F, von Kugelgen I, (2008). Involvement of basic amino acid residues in transmembrane regions 6 and 7 in agonist and antagonist recognition of the human platelet P2Y(12)-receptor. Biochem Pharmacol 76: 1201-1213.
31. Hoffmann K, Baqi Y, Morena MS, Glanzel M, Muller CE, von Kugelgen I, (2009). Interaction of new, very potent non-nucleotide antagonists with Arg256 of the human platelet P2Y12 receptor. J Pharmacol Exp Ther 331: 648-655.
32. Hohoff C, Marziniak M, Lesch KP, Deckert J, Sommer C, Mossner R, (2007). An adenosine A2A receptor gene haplotype is associated with migraine with aura. Cephalalgia 27: 177-181.
33. Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, et al. (2001). Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 409: 202-207.
34. Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, et al. (2006). Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 108: 2244-2247.
35. Johnson AD, Yanek LR, Chen MH, Faraday N, Larson MG, Tofler G, et al. (2010). Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists. Nat Genet 42: 608-613.
36. Johnson MS, Robertson DN, Holland PJ, Lutz EM, Mitchell R, (2006). Role of the conserved NPxxY motif of the 5-HT2A receptor in determining selective interaction with isoforms of ADP-ribosylation factor (ARF). Cell Signal 18: 1793-1800.
37. Jones CI, Bray S, Garner SF, Stephens J, de Bono B, Angenent WG, et al. (2009). A functional genomics approach reveals novel quantitative trait loci associated with platelet signaling pathways. Blood 114: 1405-1416.
38. Jones ML, Murden SL, Bem D, Mundell SJ, Gissen P, Daly ME, et al. (2012). Rapid genetic diagnosis of heritable platelet function disorders with next-generation sequencing: proof-of-principle with Hermansky-Pudlak syndrome. J Thromb Haemost 10: 306-309.
39. Kamae T, Kiyomizu K, Nakazawa T, Tadokoro S, Kashiwagi H, Honda S, et al. (2011). Bleeding tendency and impaired platelet function in a patient carrying a heterozygous mutation in the thromboxane A2 receptor. J Thromb Haemost 9: 1040-1048.
40. Kaplan ZS, Jackson SP, (2011). The role of platelets in atherothrombosis. Hematology Am Soc Hematol Educ Program 2011: 51-61.
41. Kunicki TJ, Williams SA, Nugent DJ, (2012). Genetic variants that affect platelet function. Curr Opin Hematol 19: 371-379.
42. Li J, Edwards PC, Burghammer M, Villa C, Schertler GF, (2004). Structure of bovine rhodopsin in a trigonal crystal form. J Mol Biol 343: 1409-1438.
43. Lordkipanidze M, Diodati JG, Palisaitis DA, Schampaert E, Turgeon J, Pharand C, (2011). Genetic determinants of response to aspirin: appraisal of 4 candidate genes. Thromb Res 128: 47-53.
44. Mao Y, Zhang L, Jin J, Ashby B, Kunapuli SP, (2010). Mutational analysis of residues important for ligand interaction with the human P2Y(12) receptor. Eur J Pharmacol 644: 10-16.
45. Marchese A, Paing MM, Temple BR, Trejo J, (2008). G protein-coupled receptor sorting to endosomes and lysosomes. Annu Rev Pharmacol Toxicol 48: 601-629.
46. Michelsen K, Yuan H, Schwappach B, (2005). Hide and run. Arginine-based endoplasmic-reticulum-sorting motifs in the assembly of heteromultimeric membrane proteins. EMBO Rep 6: 717-722.
47. Mirzadegan T, Benko G, Filipek S, Palczewski K, (2003). Sequence analyses of G-protein-coupled receptors: similarities to rhodopsin. Biochemistry 42: 2759-2767.
48. Mumford A, Nisar S, Darnige L, Jones M, Bachelot-Loza C, Gandrille S, et al. (2012). Platelet dysfunction associated with the novel Trp29Cys thromboxane A(2) receptor variant. J Thromb Haemost 11: 547-554.
49. Mumford AD, Dawood BB, Daly ME, Murden SL, Williams MD, Protty MB, et al. (2010). A novel thromboxane A2 receptor D304N variant that abrogates ligand binding in a patient with a bleeding diathesis. Blood 115: 363-369.
50. Mumford AD, Nisar S, Darnige L, Jones ML, Bachelot-Loza C, Gandrille S, et al. (2013). Platelet dysfunction associated with the novel Trp29Cys thromboxane A(2) receptor variant. J Thromb Haemost 11: 547-554.
51. Nisar S, Daly ME, Federici AB, Artoni A, Mumford AD, Watson SP, et al. (2011). An intact PDZ motif is essential for correct P2Y12 purinoceptor traffic in human platelets. Blood 118: 5641-5651.
52. Nisar SP, Cunningham M, Saxena K, Pope RJ, Kelly E, Mundell SJ, (2012). Arrestin scaffolds NHERF1 to the P2Y12 receptor to regulate receptor internalization. J Biol Chem 287: 24505-24515.
53. Nisar SP, Lordkipanidze M, Jones ML, Dawood B, Murden S, Cunningham MR, et al. (2014). A novel thromboxane A2 receptor N42S variant results in reduced surface expression and platelet dysfunction. Thromb Haemost 111: 923-932.
54. Nurden AT, Caen JP, (1974). An abnormal platelet glycoprotein pattern in three cases of Glanzmann's thrombasthenia. Br J Haematol 28: 253-260.
55. Nurden P, Savi P, Heilmann E, Bihour C, Herbert JM, Maffrand JP, et al. (1995). An inherited bleeding disorder linked to a defective interaction between ADP and its receptor on platelets. Its influence on glycoprotein IIb-IIIa complex function. J Clin Invest 95: 1612-1622.
56. Offermanns S, (2006). Activation of platelet function through G protein-coupled receptors. Circ Res 99: 1293-1304.
57. Pardo L, Deupi X, Dolker N, Lopez-Rodriguez ML, Campillo M, (2007). The role of internal water molecules in the structure and function of the rhodopsin family of G protein-coupled receptors. Chembiochem 8: 19-24.
58. Patel YM, Lordkipanidze M, Lowe GC, Nisar SP, Garner K, Stockley J, et al. (2014). A novel mutation in the P2Y12 receptor and a function-reducing polymorphism in protease-activated receptor 1 in a patient with chronic bleeding. J Thromb Haemost 12: 716-725.
59. Pawson AJ, Sharman JL, Benson HE, Faccenda E, Alexander SP, Buneman OP, et al.; NC-IUPHAR (2014). The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledge base of drug targets and their ligands. Nucl. Acids Res 42 (Database Issue): D1098-1106.
60. Poole RM, Elkinson S, (2014). Vorapaxar: first global approval. Drugs 74: 1153-1163.
61. Rao AK, Willis J, Kowalska MA, Wachtfogel YT, Colman RW, (1988). Differential requirements for platelet aggregation and inhibition of adenylate cyclase by epinephrine. Studies of a familial platelet alpha 2-adrenergic receptor defect. Blood 71: 494-501.
62. Remijn JA, IJsseldijk MJ, Strunk AL, Abbes AP, Engel H, Dikkeschei B, et al. (2007). Novel molecular defect in the platelet ADP receptor P2Y12 of a patient with haemorrhagic diathesis. Clin Chem Lab Med 45: 187-189.
63. Rivera J, Lozano ML, Navarro-Nunez L, Vicente V, (2009). Platelet receptors and signaling in the dynamics of thrombus formation. Haematologica 94: 700-711.
64. Rosenbaum DM, Rasmussen SG, Kobilka BK, (2009). The structure and function of G-protein-coupled receptors. Nature 459: 356-363.
65. Rovati GE, Capra V, Neubig RR, (2007). The highly conserved DRY motif of class A G protein-coupled receptors: beyond the ground state. Mol Pharmacol 71: 959-964.
66. Rowley JW, Oler AJ, Tolley ND, Hunter BN, Low EN, Nix DA, et al. (2011). Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood 118: e101-e111.
67. Savi P, Zachayus JL, Delesque-Touchard N, Labouret C, Herve C, Uzabiaga MF, et al. (2006). The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts. Proc Natl Acad Sci U S A 103: 11069-11074.
68. Schmidt P, Ritscher L, Dong EN, Hermsdorf T, Coster M, Wittkopf D, et al. (2013). Identification of determinants required for agonistic and inverse agonistic ligand properties at the ADP receptor P2Y12. Mol Pharmacol 83: 256-266.
69. Shiraga M, Miyata S, Kato H, Kashiwaga H, Honda S, Kurata Y, et al. (2005). Impaired platelet function in a patient with P2Y12 deficiency caused by a mutation in the translation initiation codon. J Thromb Haemost 3: 2315-2323.
70. Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, et al. (2009). Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302: 849-857.
71. Smith SM, Judge HM, Peters G, Armstrong M, Dupont A, Gaussem P, et al. (2005). PAR-1 genotype influences platelet aggregation and procoagulant responses in patients with coronary artery disease prior to and during clopidogrel therapy. Platelets 16: 340-345.
72. Smith SO, (2010). Structure and activation of the visual pigment rhodopsin. Annu Rev Biophysics 39: 309-328.
73. Stegner D, Nieswandt B, (2011). Platelet receptor signaling in thrombus formation. J Mol Med (Berl) 89: 109-121.
74. Tricoci P, Huang Z, Held C, Moliterno DJ, Armstrong PW, Van de Werf F, et al. (2012). Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 366: 20-33.
75. Watson S, Daly M, Dawood B, Gissen P, Makris M, Mundell S, et al. (2010). Phenotypic approaches to gene mapping in platelet function disorders-identification of new variant of P2Y12, TxA2 and GPVI receptors. Hamostaseologie 30: 29-38.
76. Watson SP, Auger JM, McCarty OJ, Pearce AC, (2005). GPVI and integrin alphaIIb beta3 signaling in platelets. J Thromb Haemost 3: 1752-1762.
77. Watson SP, Lowe GC, Lordkipanidze M, Morganon NV, (2013). Genotyping and phenotyping of platelet function disorders. J Thromb Haemost 11: 351-363.
78. Weinman EJ, Hall RA, Friedman PA, Liu-Chen LY, Shenolikar S, (2006). The association of NHERF adaptor proteins with g protein-coupled receptors and receptor tyrosine kinases. Annu Rev Physiol 68: 491-505.
79. Wiviott SD, Flather MD, O'Donoghue ML, Goto S, Fitzgerald DJ, Cura F, et al. (2011). Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the lessons from antagonizing the cellular effect of Thrombin-Coronary Artery Disease Trial. Circulation 123: 1854-1863.
80. Zhang J, Zhang K, Gao ZG, Paoletta S, Zhang D, Han GW, et al. (2014a). Agonist-bound structure of the human P2Y12 receptor. Nature 509: 119-122.
81. Zhang K, Zhang J, Gao ZG, Zhang D, Zhu L, Han GW, et al. (2014b). Structure of the human P2Y receptor in complex with an antithrombotic drug. Nature 509: 115-118.
82. Zhou W, Flanagan C, Ballesteros JA, Konvicka K, Davidson JS, Weinstein H, et al. (1994). A reciprocal mutation supports helix 2 and helix 7 proximity in the gonadotropin-releasing hormone receptor. Mol Pharmacol 45: 165-170.