Chaperoning G protein-coupled receptors: From cell biology to therapeutics

Endocrine Reviews

Volumn 35, Issue 4, 2014, Pages 602-647

  Tao, Ya Xiong ^a   Conn, P Michael ^b  

^a AUBURN UNIVERSITY   (United States)

^b TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHAPERONE; G PROTEIN COUPLED RECEPTOR; GONADORELIN; GUANINE NUCLEOTIDE BINDING PROTEIN; HORMONE RECEPTOR; MELANOCORTIN 4 RECEPTOR; MUTANT PROTEIN; RHODOPSIN; VASOPRESSIN V2 RECEPTOR;

CELL MATURATION; CELL MEMBRANE; CELL SURFACE; CYTOLOGY; GENE MUTATION; HUMAN; LOW TEMPERATURE; NONHUMAN; PRIORITY JOURNAL; QUALITY CONTROL; REVIEW; STRUCTURE ACTIVITY RELATION; WILD TYPE; AMINO ACID SEQUENCE; ANIMAL; DISEASE MODEL; DRUG THERAPY; GENETIC DISEASES, INBORN; GENETICS; MOLECULAR GENETICS; MUTATION; PHYSIOLOGY; PROTEIN FOLDING; TRENDS;

AMINO ACID SEQUENCE; ANIMALS; DISEASE MODELS, ANIMAL; DRUG THERAPY; GENETIC DISEASES, INBORN; HUMANS; MOLECULAR CHAPERONES; MOLECULAR SEQUENCE DATA; MUTATION; PROTEIN FOLDING; RECEPTORS, G-PROTEIN-COUPLED;

EID: 84902210360     PISSN: None     EISSN: 0163769X     Source Type: Journal    
DOI: 10.1210/er.2013-1121     Document Type: Review

References (546)

1. Foord SM, Bonner TI, Neubig RR, et al. International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev. 2005;57:279-288.
2. Davenport AP, Alexander SP, Sharman JL, et al. International Union of Basic and Clinical Pharmacology. LXXXVIII. Gprotein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol Rev. 2013; 65:967-986.
3. Fredriksson R, Lagerström MC, Lundin LG, Schiöth HB. The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol. 2003;63:1256-1272.
4. Vassilatis DK, Hohmann JG, Zeng H, et al. The G proteincoupled receptor repertoires of human and mouse. Proc Natl Acad Sci USA. 2003;100:4903-4908.
5. Bjarnadóttir TK, Gloriam DE, Hellstrand SH, Kristiansson H, Fredriksson R, Schiöth HB. Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Genomics. 2006;88:263-273.
6. Horn F, Weare J, Beukers MW, et al. GPCRDB: an information system for G protein-coupled receptors. Nucleic Acids Res. 1998;26:275-279.
7. Hall RA, Premont RT, Lefkowitz RJ. Heptahelical receptor signaling: beyond the G protein paradigm. J Cell Biol. 1999;145:927-932.
8. Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423:762-769.
9. Bockaert J, Pin JP. Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J. 1999; 18:1723-1729.
10. Yun CW, Tamaki H, Nakayama R, Yamamoto K, Kumagai H. G-Protein coupled receptor from yeast Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1997; 240:287-292.
11. Josefsson LG, Rask L. Cloning of a putative G-proteincoupled receptor from Arabidopsis thaliana. Eur J Biochem. 1997;249:415-420.
12. Hill CA, Fox AN, Pitts RJ, et al. G protein-coupled receptors in Anopheles gambiae. Science. 2002;298:176-178.
13. Rockman HA, Koch WJ, Lefkowitz RJ. Seven-transmembrane-spanning receptors and heart function. Nature. 2002;415:206-212.
14. Maguire JJ, Davenport AP. Regulation of vascular reactivity by established and emerging GPCRs. Trends Pharmacol Sci. 2005;26:448-454.
15. Ahrén B. IsletGprotein-coupled receptors as potential targets for treatment of type 2 diabetes. Nat Rev Drug Discov. 2009;8:369-385.
16. Tao YX, Yuan ZH, Xie J. G Protein-coupled receptors as regulators of energy homeostasis. ProgMolBiol Transl Sci. 2013;114:1-43.
17. Tao YX, Liang XF. G Protein-coupled receptors as regulators of glucose homeostasis and therapeutic targets for diabetes mellitus. Prog Mol Biol Transl Sci. 2014; 121:1-21.
18. Ulloa-Aguirre A, Zariñán T, Dias JA, Conn PM. Mutations in G protein-coupled receptors that impact receptor trafficking and reproductive function. Mol Cell Endocrinol. 2014;382:411-423.
19. Dorsam RT, Gutkind JS. G-Protein-coupled receptors and cancer. Nat Rev Cancer. 2007;7:79-94.
20. O'Hayre M, Vázquez-Prado J, Kufareva I, et al. The emerging mutational landscape ofGproteins and G-protein-coupled receptors in cancer. Nat Rev Cancer. 2013;13:412-424.
21. Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science. 2005;307: 1625-1630.
22. Thomas P. Rapid steroid hormone actions initiated at the cell surface and the receptors that mediate them with an emphasis on recent progress in fish models. Gen Comp Endocrinol. 2012;175:367-383.
23. Flower DR. Modelling G-protein-coupled receptors for drug design. Biochim Biophys Acta. 1999;1422:207-234.
24. Palczewski K, Kumasaka T, Hori T, et al. Crystal structure of rhodopsin: a Gprotein-coupled receptor. Science. 2000; 289:739-745.
25. 2 adrenergic G-protein-coupled receptor. Nature. 2007;450:383-387.
26. 2-adrenergic receptor function. Science. 2007;318:1266-1273.
27. Hanson MA, Roth CB, Jo E, et al. Crystal structure of a lipid G protein-coupled receptor. Science. 2012;335:851-855.
28. Ichimura A, Hirasawa A, Poulain-Godefroy O, et al. Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature. 2012;483:350-354.
29. Tadevosyan A, Vaniotis G, Allen BG, et al. G proteincoupled receptor signalling in the cardiac nuclear membrane: evidence and possible roles in physiological and pathophysiological function. J Physiol. 2012;590:1313-1330.
30. Bénard G, Massa F, Puente N, et al. Mitochondrial CB1 receptors regulate neuronal energy metabolism. Nat Neurosci. 2012;15:558-564.
31. Nanoff C, Freissmuth M. ER-bound steps in the biosynthesis of G protein-coupled receptors. Subcell Biochem. 2012;63:1-21.
32. Ferguson SS. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev. 2001;53:1-24.
33. Lefkowitz RJ. A brief history of G-protein coupled recepdoi: ors (Nobel lecture). Angew Chem Int Ed Engl. 2013;52: 6366-6378.
34. Tan CM, Brady AE, Nickols HH, Wang Q, Limbird LE. Membrane trafficking of G protein-coupled receptors. Annu Rev Pharmacol Toxicol. 2004;44:559-609.
35. Chesterton CJ. Distribution of cholesterol precursors and other lipids among rat liver intracellular structures. J Biol Chem. 1968;243:1147-1151.
36. Lam AK, Galione A. The endoplasmic reticulum and junctional membrane communication during calcium signaling. Biochim Biophys Acta. 2013;1833:2542-2559.
37. Blobel G. Protein targeting (Nobel lecture). Chembiochem. 2000;1:86-102.
38. Sitia R, Braakman I. Quality control in the endoplasmic reticulum protein factory. Nature. 2003;426:891-894.
39. Braakman I, Bulleid NJ. Protein folding and modification in the mammalian endoplasmic reticulum. Annu Rev Biochem. 2011;80:71-99.
40. Hartl FU, Bracher A, Hayer-Hartl M. Molecular chaperones in protein folding and proteostasis. Nature. 2011; 475:324-332.
41. Guerriero CJ, Brodsky JL. The delicate balance between secreted protein folding and endoplasmic reticulum-associated degradation in human physiology. Physiol Rev. 2012;92:537-576.
42. Malhotra JD, Miao H, Zhang K, et al. Antioxidants reduce endoplasmic reticulum stress and improve protein secretion. Proc Natl Acad Sci USA. 2008;105:18525-18530.
43. Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011; 334:1081-1086.
44. Flynn GC, Pohl J, Flocco MT, Rothman JE. Peptide-binding specificity of the molecular chaperone BiP. Nature. 1991;353:726-730.
45. Otero JH, Lizák B, Hendershot LM. Life and death of a BiP substrate. Semin Cell Dev Biol. 2010;21:472-478.
46. Hebert DN, Molinari M. Flagging and docking: dual roles for N-glycans in protein quality control and cellular proteostasis. Trends Biochem Sci. 2012;37:404-410.
47. Helenius A, Aebi M. Intracellular functions of N-linked glycans. Science. 2001;291:2364-2369.
48. Kanehara K, Kawaguchi S, Ng DT. TheEDEMand Yos9p families of lectin-like ERAD factors. Semin Cell Dev Biol. 2007;18:743-750.
49. Khorana HG. Rhodopsin, photoreceptor of the rod cell.An emerging pattern for structure and function. J Biol Chem. 1992;267:1-4.
50. Laduron P. Axoplasmic transport of muscarinic receptors. Nature. 1980;286:287-288.
51. Young WS 3rd, Wamsley JK, Zarbin MA, Kuhar MJ. Opioid receptors undergo axonal flow. Science. 1980;210:76-78.
52. Petaja-Repo UE, Hogue M, Laperriere A, Walker P, Bouvier M. Export from the endoplasmic reticulum represents the limiting step in the maturation and cell surface expression of the human δ opioid receptor. J Biol Chem. 2000; 275:13727-13736.
53. Bermak JC, Li M, Bullock C, Zhou QY. Regulation of transport of the dopamine D1 receptor by a new membrane-associated ER protein. Nat Cell Biol. 2001;3:492-498.
54. Petaja-Repo UE, Hogue M, Laperriere A, Bhalla S, Walker P, Bouvier M. Newly synthesized human delta opioid receptors retained in the endoplasmic reticulum are retrotranslocated to the cytosol, deglycosylated, ubiquitinated, and degraded by the proteasome. J Biol Chem. 2001;276: 4416-4423.
55. Cornea-Hébert V, Watkins KC, Roth BL, et al. Similar ultrastructural distribution of the 5-HT(2A) serotonin receptor and microtubule-associated protein MAP1A in cortical dendrites of adult rat. Neuroscience. 2002;113: 23-35.
56. Doherty MD, Pickel VM. Ultrastructural localization of the serotonin 2A receptor in dopaminergic neurons in the ventral tegmental area. Brain Res. 2000;864:176-185.
57. Pietilä EM, Tuusa JT, Apaja PM, et al. Inefficient maturation of the rat luteinizing hormone receptor. A putative way to regulate receptor numbers at the cell surface. J Biol Chem. 2005;280:26622-26629.
58. Misrahi M, Ghinea N, Sar S, et al. Processing of the precursors of the human thyroid-stimulating hormone receptor in various eukaryotic cells (human thyrocytes, transfected L cells and baculovirus-infected insect cells). Eur J Biochem. 1994;222:711-719.
59. Yu R, Hinkle PM. Effect of cell type on the subcellular localization of the thyrotropin-releasing hormone receptor. Mol Pharmacol. 1997;51:785-793.
60. Dermer SJ, Cohen DP, Thaw CN, Nussenzveig DR, Gershengorn MC. Intracellular retention and rapid degradation of human calcitonin receptors overexpressed in COS cells. Endocrinology. 1996;137:5502-5508.
61. McClintock TS, Landers TM, Gimelbrant AA, et al. Functional expression of olfactory-adrenergic receptor chimeras and intracellular retention of heterologously expressed olfactory receptors. Brain Res Mol Brain Res. 1997;48: 270-278.
62. Gimelbrant AA, Stoss TD, Landers TM, McClintock TS. Truncation releases olfactory receptors from the endoplasmic reticulum of heterologous cells. J Neurochem. 1999; 72:2301-2311.
63. Moriyama K, Sitkovsky MV. Adenosine A2A receptor is involved in cell surface expression of A2B receptor. J Biol Chem. 2010;285:39271-39288.
64. von Zastrow M, Link R, Daunt D, Barsh G, Kobilka B. Subtype-specific differences in the intracellular sorting ofG protein-coupled receptors. J Biol Chem. 1993;268:763-766.
65. Tao YX. Functional characterization of novel melanocortin-3 receptor mutations identified from obese subjects. Biochim Biophys Acta. 2007;1772:1167-1174.
66. Fishburn CS, Elazar Z, Fuchs S. Differential glycosylation and intracellular trafficking for the long and short isoforms of the D2 dopamine receptor. J Biol Chem. 1995;270: 29819-29824.
67. Hasegawa H, Katoh H, Yamaguchi Y, Nakamura K, Futakawa S, Negishi M. Different membrane targeting of prostaglandin EP3 receptor isoforms dependent on their carboxy-terminal tail structures. FEBS Lett. 2000;473: 76-80.
68. Wellendorph P, Bräuner-Osborne H. Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family CG-protein-coupled receptor. Gene. 2004;335:37-46.
69. Wellendorph P, Hansen KB, Balsgaard A, Greenwood JR, Egebjerg J, Bräuner-Osborne H. Deorphanization of GPRC6A: a promiscuous L-α-amino acid receptor with preference for basic amino acids. Mol Pharmacol. 2005; 67:589-597.
70. Ascoli M, Fanelli F, Segaloff DL. The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr Rev. 2002;23:141-174.
71. Lin CC, Clouser C, Peegel H, Menon B, Menon KM. The extracellular domain of luteinizing hormone receptor dictates its efficiency of maturation. Biochem Biophys Res Commun. 2008;377:307-311.
72. Oksche A, Leder G, Valet S, et al. Variant amino acids in the extracellular loops of murine and human vasopressin V2 receptors account for differences in cell surface expression and ligand affinity. Mol Endocrinol. 2002;16:799-813.
73. Holtbäck U, Brismar H, DiBona GF, Fu M, Greengard P, Aperia A. Receptor recruitment: a mechanism for interactions between G protein-coupled receptors. Proc Natl Acad Sci USA. 1999;96:7271-7275.
74. Lin X, Janovick JA, Brothers S, Blömenrohr M, Bogerd J, Conn PM. Addition of catfish gonadotropin-releasing hormone (GnRH) receptor intracellular carboxyl-terminal tail to rat GnRH receptor alters receptor expression and regulation. Mol Endocrinol. 1998;12:161-171.
75. Conn PM, Janovick JA, Brothers SP, Knollman PE. 'Effective inefficiency': cellular control of protein trafficking as a mechanism of post-translational regulation. J Endocrinol. 2006;190:13-16.
76. Apaja PM, Aatsinki JT, Rajaniemi HJ, Petäjä-Repo UE. Expression of the mature luteinizing hormone receptor in rodent urogenital and adrenal tissues is developmentally regulated at a posttranslational level. Endocrinology. 2005;146:3224-3232.
77. 2C-adrenoceptor translocation to the cell surface of microvascular smooth muscle cells. Am J Physiol Cell Physiol. 2012;303:C499-C511.
78. Cheng PY, Svingos AL, Wang H, et al. Ultrastructural immunolabeling shows prominent presynaptic vesicular localization of δ-opioid receptor within both enkephalinand nonenkephalin-containing axon terminals in the superficial layers of the rat cervical spinal cord. J Neurosci. 1995;15:5976-5988.
79. Zhang X, Bao L, Arvidsson U, Elde R, Hökfelt T. Localization and regulation of the δ-opioid receptor in dorsal root ganglia and spinal cord of the rat and monkey: evidence for association with the membrane of large densecore vesicles. Neuroscience. 1998;82:1225-1242.
80. Cahill CM, Holdridge SV, Morinville A. Trafficking of δ-opioid receptors and other G-protein-coupled receptors: implications for pain and analgesia. Trends Pharmacol Sci. 2007;28:23-31.
81. Zhang X, Bao L, Guan JS. Role of delivery and trafficking of δ-opioid peptide receptors in opioid analgesia and tolerance. Trends Pharmacol Sci. 2006;27:324-329.
82. Bao L, Jin SX, Zhang C, et al. Activation of δ opioid receptors induces receptor insertion and neuropeptide secretion. Neuron. 2003;37:121-133.
83. Brismar H, Asghar M, Carey RM, Greengard P, Aperia A. Dopamine-induced recruitment of dopamine D1 receptors to the plasma membrane. Proc Natl Acad Sci USA. 1998; 95:5573-5578.
84. Shimizu S, Brown M, Sengupta R, Penfold ME, Meucci O. CXCR7 protein expression in human adult brain and differentiated neurons. PLoS One. 2011;6:e20680.
85. Rajagopal S, Kim J, Ahn S, et al. β-arrestin-but not G protein-mediated signaling by the "decoy" receptor CXCR7. Proc Natl Acad Sci USA. 2010;107:628-632.
86. Boldajipour B, Mahabaleshwar H, Kardash E, et al. Control of chemokine-guided cell migration by ligand sequestration. Cell. 2008;132:463-473.
87. Blackburn PE, Simpson CV, Nibbs RJ, et al. Purification and biochemical characterization of the D6 chemokine receptor. Biochem J. 2004;379:263-272.
88. Bonecchi R, Borroni EM, Anselmo A, et al. Regulation of D6 chemokine scavenging activity by ligand-and Rab11-dependent surface up-regulation. Blood. 2008;112:493-503.
89. Breitwieser GE. Minireview: the intimate link between calcium sensing receptor trafficking and signaling: implications for disorders of calcium homeostasis. Mol Endocrinol. 2012;26:1482-1495.
90. Grant MP, Stepanchick A, Cavanaugh A, Breitwieser GE. Agonist-driven maturation and plasma membrane insertion of calcium-sensing receptors dynamically control signal amplitude. Sci Signal. 2011;4:ra78.
91. Grant MP, Stepanchick A, Breitwieser GE. Calcium signaling regulates trafficking of familial hypocalciuric hypercalcemia (FHH) mutants of the calcium sensing receptor. Mol Endocrinol. 2012;26:2081-2091.
92. Jong YJ, Kumar V, O'Malley KL. Intracellular metabotropic glutamate receptor 5 (mGluR5) activates signaling cascades distinct from cell surface counterparts. J Biol Chem. 2009;284:35827-35838.
93. Kumar V, Fahey PG, Jong YJ, Ramanan N, O'Malley KL. Activation of intracellular metabotropic glutamate receptor 5 in striatal neurons leads to up-regulation of genes associated with sustained synaptic transmission including Arc/Arg3.1 protein. J Biol Chem. 2012;287:5412-5425.
94. Granell S, Molden BM, Baldini G. Exposure of MC4R to agonist in the endoplasmic reticulum stabilizes an active conformation of the receptor that does not desensitize. Proc Natl Acad Sci USA. 2013;110:E4733-E4742.
95. Calebiro D, Nikolaev VO, Gagliani MC, et al. Persistent cAMP-signals triggered by internalized G-protein-coupled receptors. PLoS Biol. 2009;7:e1000172.
96. Ferrandon S, Feinstein TN, Castro M, et al. Sustained cyclicAMPproduction by parathyroid hormone receptor endocytosis. Nat Chem Biol. 2009;5:734-742.
97. Feinstein TN, Wehbi VL, Ardura JA, et al. Retromer terminates the generation of cAMP by internalized PTH receptors. Nat Chem Biol. 2011;7:278-284.
98. Werthmann RC, Volpe S, Lohse MJ, Calebiro D. Persistent cAMP signaling by internalized TSH receptors occurs in thyroid but not in HEK293 cells. FASEB J. 2012;26:2043-2048.
99. Irannejad R, Tomshine JC, Tomshine JR, et al. Confordoi: mational biosensors reveal GPCR signalling from endosomes. Nature. 2013;495:534-538.
100. Lohse MJ, Calebiro D. Cell biology: receptor signals come in waves. Nature. 2013;495:457-458.
101. Nathans J, Hogness DS. Isolation, sequence analysis, and intron-exon arrangement of the gene encoding bovine rhodopsin. Cell. 1983;34:807-814.
102. Dixon RA, Kobilka BK, Strader DJ, et al. Cloning of the gene and cDNA for mammalian β-adrenergic receptor and homology with rhodopsin. Nature. 1986;321:75-79.
103. Spiegel AM. Defects in G protein-coupled signal transduction in human disease. Annu Rev Physiol. 1996;58:143-170.
104. Schöneberg T, Schulz A, Gudermann T. The structural basis of G-protein-coupled receptor function and dysfunction inhumandiseases. Rev Physiol Biochem Pharmacol. 2002; 144:143-227.
105. Spiegel AM, Weinstein LS. Inherited diseases involving G proteins and Gprotein-coupled receptors. Annu Rev Med. 2004;55:27-39.
106. Schöneberg T, Schulz A, Biebermann H, Hermsdorf T, Römpler H, Sangkuhl K. Mutant G-protein-coupled receptors as a cause of human diseases. Pharmacol Ther. 2004;104:173-206.
107. Tao YX. Inactivating mutations of G protein-coupled receptors and diseases: structure-function insights and therapeutic implications. Pharmacol Ther. 2006;111:949-973.
108. Conn PM, Ulloa-Aguirre A, Ito J, Janovick JA. G proteincoupled receptor trafficking in health and disease: lessons learned to prepare for therapeutic mutant rescue in vivo. Pharmacol Rev. 2007;59:225-250.
109. Tao YX. Constitutive activation of G protein-coupled receptors and diseases: insights into mechanisms of activation and therapeutics. Pharmacol Ther. 2008;120:129-148.
110. Vassart G, Costagliola S. G protein-coupled receptors: mutations and endocrine diseases. Nat Rev Endocrinol. 2011; 7:362-372.
111. Metallinos DL, Bowling AT, Rine J. A missense mutation in the endothelin-B receptor gene is associated with Lethal White Foal Syndrome: an equine version of Hirschsprung disease. Mamm Genome. 1998;9:426-431.
112. Yang GC, Croaker D, Zhang AL, Manglick P, Cartmill T, Cass D. A dinucleotide mutation in the endothelin-B receptor gene is associated with lethal white foal syndrome (LWFS); a horse variant of Hirschsprung disease. Hum Mol Genet. 1998;7:1047-1052.
113. Kijas JW, Cideciyan AV, Aleman TS, et al. Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa. Proc Natl Acad Sci USA. 2002;99: 6328-6333.
114. Lin L, Faraco J, Li R, et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 1999;98:365-376.
115. Kim KS, Larsen N, Short T, Plastow G, Rothschild MF. A missense variant of the porcine melanocortin-4 receptor (MC4R) gene is associated with fatness, growth, and feed intake traits. Mamm Genome. 2000;11:131-135.
116. Fan ZC, Sartin JL, Tao YX. Pharmacological analyses of two naturally occurring porcine melanocortin-4 receptor mutations in domestic pigs. Domest Anim Endocrinol. 2008;34:383-390.
117. Skorczyk A, Stachowiak M, Szczerbal I, et al. Polymorphism and chromosomal location of the MC4R (melanocortin-4 receptor) gene in the dog and red fox. Gene. 2007; 392:247-252.
118. Yan J, Tao YX. Pharmacological characterization of canine melancortin-4 receptor and its natural variant V213F. Domest Anim Endocrinol. 2011;41:91-97.
119. KuhmannSE, Platt EJ, Kozak SL, Kabat D. Polymorphisms in the CCR5 genes of African green monkeys and mice implicate specific amino acids in infections by simian and human immunodeficiency viruses. J Virol. 1997;71:8642-8656.
120. Cone RD, Lu D, Koppula S, et al. The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Recent Prog Horm Res. 1996;51:287-317.
121. Rana BK, Shiina T, Insel PA. Genetic variations and polymorphisms of Gprotein-coupled receptors: functional and therapeutic implications. Annu Rev Pharmacol Toxicol. 2001;41:593-624.
122. Insel PA, Tang CM, Hahntow I, Michel MC. Impact of GPCRs in clinical medicine: monogenic diseases, genetic variants and drug targets. Biochim Biophys Acta. 2007; 1768:994-1005.
123. Foord SM. Receptor classification: post genome. Curr Opin Pharmacol. 2002;2:561-566.
124. Li X, Li W, Wang H, et al. Pseudogenization of a sweetreceptor gene accounts for cats' indifference toward sugar. PLoS Genet. 2005;1:27-35.
125. Jiang P, Josue J, Li X, et al. Major taste loss in carnivorous mammals. Proc Natl Acad Sci USA. 2012;109:4956-4961.
126. Li R, Fan W, Tian G, et al. The sequence and de novo assembly of the giant panda genome. Nature. 2010;463: 311-317.
127. Tao YX, Segaloff DL. Functional characterization of melanocortin-4 receptor mutations associated with childhood obesity. Endocrinology. 2003;144:4544-4551.
128. Tao YX. Molecular mechanisms of the neural melanocortin receptor dysfunction in severe early onset obesity. Mol Cell Endocrinol. 2005;239:1-14.
129. Schiaffino MV, Baschirotto C, Pellegrini G, et al. The ocular albinism type 1 gene product is a membrane glycoprotein localized to melanosomes. Proc Natl Acad Sci USA. 1996;93:9055-9060.
130. Schiaffino MV, d'Addio M, Alloni A, et al. Ocular albinism: evidence for a defect in an intracellular signal transduction system. Nat Genet. 1999;23:108-112.
131. Palmisano I, Bagnato P, Palmigiano A, et al. The ocular albinism type 1 protein, an intracellularGprotein-coupled receptor, regulates melanosome transport in pigment cells. Hum Mol Genet. 2008;17:3487-3501.
132. d'Addio M, Pizzigoni A, Bassi MT, et al. Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1. Hum Mol Genet. 2000;9:3011-3018.
133. Salahpour A, Angers S, Mercier JF, Lagacé M, Marullo S, Bouvier M. Homodimerization of the β2-adrenergic re-ceptor as a prerequisite for cell surface targeting. J Biol Chem. 2004;279:33390-33397.
134. Rajan RS, Kopito RR. Suppression of wild-type rhodopsin maturation by mutants linked to autosomal dominant retinitis pigmentosa. J Biol Chem. 2005;280:1284-1291.
135. Duvernay MT, Filipeanu CM, Wu G. The regulatory mechanisms of export trafficking of G protein-coupled receptors. Cell Signal. 2005;17:1457-1465.
136. Kurada P, O'Tousa JE. Retinal degeneration caused by dominant rhodopsin mutations in Drosophila. Neuron. 1995;14:571-579.
137. Zhu X, Wess J. Truncated V2 vasopressin receptors as negative regulators of wild-type V2 receptor function. Biochemistry. 1998;37:15773-15784.
138. Benkirane M, Jin DY, Chun RF, Koup RA, Jeang KT. Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by ccr5Δ32. J Biol Chem. 1997;272: 30603-30606.
139. Tao YX, Johnson NB, Segaloff DL. Constitutive and agonist-dependent self-association of the cell surface human lutropin receptor. J Biol Chem. 2004;279:5904-5914.
140. Calebiro D, de Filippis T, Lucchi S, et al. Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance. Hum Mol Genet. 2005;14:2991-3002.
141. Beaumont KA, Newton RA, Smit DJ, Leonard JH, Stow JL, Sturm RA. Altered cell surface expression of human MC1Rvariant receptor alleles associated with red hair and skin cancer risk. Hum Mol Genet. 2005;14:2145-2154.
142. Brothers SP, Cornea A, Janovick JA, Conn PM. Human loss-of-function gonadotropin-releasing hormone receptor mutants retain wild-type receptors in the endoplasmic reticulum: molecular basis of the dominant-negative effect. Mol Endocrinol. 2004;18:1787-1797.
143. Ibrahim S, Tetruashvily M, Frey AJ, et al. Dominant negative actions of human prostacyclin receptor variant through dimerization: implications for cardiovascular disease. Arterioscler Thromb Vasc Biol. 2010;30:1802-1809.
144. Kaykas A, Yang-Snyder J, Héroux M, Shah KV, Bouvier M, Moon RT. Mutant Frizzled 4 associated with vitreoretinopathy traps wild-type Frizzled in the endoplasmic reticulum by oligomerization. Nat Cell Biol. 2004; 6:52-58.
145. Lubrano-Berthelier C, Durand E, Dubern B, et al. Intracellular retention is a common characteristic of childhood obesity-associated MC4R mutations. Hum Mol Genet. 2003;12:145-153.
146. Yeo GS, Lank EJ, Farooqi IS, Keogh J, Challis BG, O'Rahilly S. Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms. Hum Mol Genet. 2003;12:561-574.
147. Nijenhuis WA, Garner KM, van Rozen RJ, Adan RA. Poor cell surface expression of human melanocortin-4 receptor mutations associated with obesity. J BiolChem. 2003;278: 22939-22945.
148. Tao YX. Mutations in melanocortin-4 receptor and human obesity. Prog Mol Biol Transl Sci. 2009;88:173-204.
149. Biebermann H, Krude H, Elsner A, Chubanov V, Gudermann T, Grüters A. Autosomal-dominant mode of inheritance of a melanocortin-4 receptor mutation in a patient with severe early-onset obesity is due to a dominant-negative effect caused by receptor dimerization. Diabetes. 2003;52:2984-2988.
150. Tao YX. Mutations in the melanocortin-3 receptor (MC3R) gene: impact on human obesity or adiposity. Curr Opin Investig Drugs. 2010;11:1092-1096.
151. Tao YX, Segaloff DL. Functional characterization of melanocortin-3 receptor variants identify a loss-of-function mutation involving an amino acid critical for G proteincoupled receptor activation. J Clin Endocrinol Metab. 2004;89:3936-3942.
152. Yang F, Tao YX. Functional characterization of nine novel naturally occurring human melanocortin-3 receptor mutations. Biochim Biophys Acta. 2012;1822:1752-1761.
153. Mandrika I, Petrovska R, Wikberg J. Melanocortin receptors form constitutive homo-and heterodimers. Biochem Biophys Res Commun. 2005;326:349-354.
154. Bulenger S, Marullo S, Bouvier M. Emerging role of homoand heterodimerization in G-protein-coupled receptor biosynthesis and maturation. Trends Pharmacol Sci. 2005; 26:131-137.
155. Monnier C, Dodé C, Fabre L, et al. PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity. Hum Mol Genet. 2009;18: 75-81.
156. Zhu L, Imanishi Y, Filipek S, et al. Autosomal recessive retinitis pigmentosa and E150K mutation in the opsin gene. J Biol Chem. 2006;281:22289-22298.
157. Gimelbrant AA, Haley SL, McClintock TS. Olfactory receptor trafficking involves conserved regulatory steps. J Biol Chem. 2001;276:7285-7290.
158. 2-adrenergic receptors by theNtermini at multiple intracellular compartments. J Biol Chem. 2006;281:38543-38554.
159. Hermosilla R, Oueslati M, Donalies U, et al. Disease-causing V2 vasopressin receptors are retained in different compartments of the early secretory pathway. Traffic. 2004; 5:993-1005.
160. Krebs MP, Noorwez SM, Malhotra R, Kaushal S. Quality control of integral membrane proteins. Trends Biochem Sci. 2004;29:648-655.
161. Dong C, Filipeanu CM, Duvernay MT, Wu G. Regulation of G protein-coupled receptor export trafficking. Biochim Biophys Acta. 2007;1768:853-870.
162. 2B-adrenergic receptor: structural basis, roles of small GTPases. CurrTop Membr. 2011;67:79-100.
163. Anfinsen CB. Principles that govern the folding of protein chains. Science. 1973;181:223-230.
164. Dill KA, MacCallum JL. The protein-folding problem, 50 years on. Science. 2012;338:1042-1046.
165. Gidalevitz T, Stevens F, Argon Y. Orchestration of secretory protein folding by ER chaperones. Biochim Biophys Acta. 2013;1833:2410-2424.
166. Jaenicke R. Protein folding: local structures, domains, subunits, and assemblies. Biochemistry. 1991;30:3147-3161.
167. Cheng MY, Hartl FU, Martin J, et al. Mitochondrial heatshock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature. 1989;337: 620-625.
168. Caramelo JJ, Parodi AJ. Getting in and out from calnexin/ calreticulin cycles. J Biol Chem. 2008;283:10221-10225.
169. Saito Y, Ihara Y, Leach MR, Cohen-Doyle MF, Williams DB. Calreticulin functions in vitro as a molecular chaperone for both glycosylated and non-glycosylated proteins. EMBO J. 1999;18:6718-6729.
170. Swanton E, High S, Woodman P. Role of calnexin in the glycan-independent quality control of proteolipid protein. EMBO J. 2003;22:2948-2958.
171. Williams DB. Beyond lectins: the calnexin/calreticulin chaperone system of the endoplasmic reticulum. J Cell Sci. 2006;119:615-623.
172. Stiles GL, Benovic JL, Caron MG, Lefkowitz RJ. Mammalian β-adrenergic receptors. Distinct glycoprotein populations containing high mannose or complex type carbohydrate chains. J Biol Chem. 1984;259:8655-8663.
173. George ST, Ruoho AE, Malbon CC. N-Glycosylation in expression and function of β-adrenergic receptors. J Biol Chem. 1986;261:16559-16564.
174. Benovic JL, Staniszewski C, Cerione RA, Codina J, Lefkowitz RJ, Caron MG. The mammalian β-adrenergic receptor: structural and functional characterization of the carbohydrate moiety. J Recept Res. 1987;7:257-281.
175. Davis DP, Rozell TG, Liu X, Segaloff DL. The six N-linked carbohydrates of the lutropin/choriogonadotropin receptor are not absolutely required for correct folding, cell surface expression, hormone binding, or signal transduction. Mol Endocrinol. 1997;11:550-562.
176. Davis D, Liu X, Segaloff DL. Identification of the sites of N-linked glycosylation on the follicle-stimulating hormone (FSH) receptor and assessment of their role in FSH receptor function. Mol Endocrinol. 1995;9:159-170.
177. Rozell TG, Davis DP, Chai Y, Segaloff DL. Association of gonadotropin receptor precursors with the protein folding chaperone calnexin. Endocrinology. 1998;139:1588-1593.
178. Mizrachi D, Segaloff DL. Intracellularly located misfolded glycoprotein hormone receptors associate with different chaperone proteins than their cognate wild-type receptors. Mol Endocrinol. 2004;18:1768-1777.
179. Siffroi-Fernandez S, Giraud A, Lanet J, Franc JL. Association of the thyrotropin receptor with calnexin, calreticulin and BiP. Effects on the maturation of the receptor. Eur J Biochem. 2002;269:4930-4937.
180. Brothers SP, Janovick JA, Conn PM. Calnexin regulated gonadotropin-releasing hormone receptor plasma membrane expression. J Mol Endocrinol. 2006;37:479-488.
181. Morello JP, Salahpour A, Petäjä-Repo UE, et al. Association of calnexin with wild type and mutant AVPR2 that causes nephrogenic diabetes insipidus. Biochemistry. 2001;40:6766-6775.
182. 2 dopamine receptor expression is regulated by direct interaction with the chaperone protein calnexin. J Biol Chem. 2007;282:21285-21300.
183. Fan J, Perry SJ, Gao Y, Schwarz DA, Maki RA. A point mutation in the human melanin concentrating hormone receptor 1 reveals an important domain for cellular trafficking. Mol Endocrinol. 2005;19:2579-2590.
184. Cabrera-Wrooman A, Janovick JA, Conn PM. Species sequence differences determine the interaction of GnRH receptor with the cellular quality control system. Mol Cell Endocrinol. 2013;381:1-7.
185. Butz JA, Niebauer RT, Robinson AS. Co-expression of molecular chaperones does not improve the heterologous expression of mammalian G-protein coupled receptor expression in yeast. Biotechnol Bioeng. 2003;84:292-304.
186. Markkanen PM, Petäjä-Repo UE. N-Glycan-mediated quality control in the endoplasmic reticulum is required for the expression of correctly folded δ-opioid receptors at the cell surface. J Biol Chem. 2008;283:29086-29098.
187. Lanctôt PM, Leclerc PC, Escher E, Guillemette G, Leduc R. Role of N-glycan-dependent quality control in the cellsurface expression of the AT1 receptor. Biochem Biophys Res Commun. 2006;340:395-402.
188. 2+ regulation, and photoreceptor cell survival. Neuron. 2006;49:229-241.
189. Kosmaoglou M, Cheetham ME. Calnexin is not essential for mammalian rod opsin biogenesis. Mol Vis. 2008;14: 2466-2474.
190. Noorwez SM, Sama RR, Kaushal S. Calnexin improves the folding efficiency of mutant rhodopsin in the presence of pharmacological chaperone 11-cis-retinal. J Biol Chem. 2009;284:33333-33342.
191. 2+ response of vertebrate olfactory receptors. Chem Senses. 2009;34:15-23.
192. Matsunami H, Amrein H. Taste and pheromone perception in mammals and flies. Genome Biol. 2003;4:220.
193. Dey S, Matsunami H. Calreticulin chaperones regulate functional expression of vomeronasal type 2 pheromone receptors. Proc Natl Acad Sci USA. 2011;108:16651-16656.
194. Parent A, Roy SJ, Iorio-Morin C, et al.ANKRD13Cacts as a molecular chaperone for G protein-coupled receptors. J Biol Chem. 2010;285:40838-40851.
195. Lindquist S. The heat-shock response. Annu Rev Biochem. 1986;55:1151-1191.
196. Langer T, Lu C, Echols H, Flanagan J, Hayer MK, Hartl FU. Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding. Nature. 1992;356:683-689.
197. Frydman J, Nimmesgern E, Ohtsuka K, Hartl FU. Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones. Nature. 1994;370: 111-117.
198. Lim WK, Kanelakis KC, Neubig RR. Regulation of G protein signaling by the 70kDa heat shock protein. Cell Signal. 2013;25:389-396.
199. Bergmayr C, Thurner P, Keuerleber S, et al. Recruitment of a cytoplasmic chaperone relay by the A2A adenosine receptor. J Biol Chem. 2013;288:28831-28844.
200. Filipeanu CM, de Vries R, Danser AH, Kapusta DR. Modulation of α2C adrenergic receptor temperature-sensitive trafficking by HSP90. Biochim Biophys Acta. 2011;1813: 346-357.
201. Meimaridou E, Gooljar SB, Ramnarace N, Anthonypillai L, Clark AJ, Chapple JP. The cytosolic chaperone Hsc70 promotes traffic to the cell surface of intracellular retained melanocortin-4 receptor mutants. Mol Endocrinol. 2011; 25:1650-1660.
202. Kogure K, Nakamura K, Ikeda S, et al. Glucose-regulated protein, 78-kilodalton is a modulator of luteinizing hormone receptor expression in luteinizing granulosa cells in rats. Biol Reprod. 2013;88:8.
203. Gorbatyuk MS, Knox T, LaVail MM, et al. Restoration of visual function in P23H rhodopsin transgenic rats by gene delivery of BiP/Grp78. Proc Natl Acad Sci USA. 2010;107: 5961-5966.
204. Liu X, Garriga P, Khorana HG. Structure and function in rhodopsin: correct folding and misfolding in two point mutants in the intradiscal domain of rhodopsin identified in retinitis pigmentosa. Proc Natl Acad Sci USA. 1996;93: 4554-4559.
205. Lin JH, Li H, Yasumura D, et al. IRE1 signaling affects cell fate during the unfolded protein response. Science. 2007; 318:944-949.
206. Leskelä TT, Lackman JJ, VierimaaMM,et al. Cys-27 variant of human δ-opioid receptor modulates maturation and cell surface delivery of Phe-27 variant via heteromerization. J Biol Chem. 2012;287:5008-5020.
207. Dryja TP, Hahn LB, Cowley GS, McGee TL, Berson EL. Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa. Proc Natl Acad Sci USA. 1991;88:9370-9374.
208. Olsson JE, Gordon JW, Pawlyk BS, et al. Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa. Neuron. 1992; 9:815-830.
209. Athanasiou D, Kosmaoglou M, Kanuga N, et al. BiP prevents rod opsin aggregation. MolBiol Cell. 2012;23:3522-3531.
210. Pai KS, Mahajan VB, Lau A, Cunningham DD. Thrombin receptor signaling to cytoskeleton requires Hsp90. J Biol Chem. 2001;276:32642-32647.
211. Pratt WB.The role of the hsp90-based chaperone system in signal transduction by nuclear receptors and receptors signaling via MAP kinase. Annu Rev Pharmacol Toxicol. 1997;37:297-326.
212. Fass D. Disulfide bonding in protein biophysics. Annu Rev Biophys. 2012;41:63-79.
213. Tu BP, Weissman JS. Oxidative protein folding in eukaryotes: mechanisms and consequences. J Cell Biol. 2004; 164:341-346.
214. Riemer J, Bulleid N, Herrmann JM. Disulfide formation in the ER and mitochondria: two solutions to a common process. Science. 2009;324:1284-1287.
215. Alon A, Grossman I, Gat Y, et al. The dynamic disulphide relay of quiescin sulphydryl oxidase. Nature. 2012;488: 414-418.
216. Goldberger RF, Epstein CJ, Anfinsen CB. Purification and properties of a microsomal enzyme system catalyzing the reactivation of reduced ribonuclease and lysozyme. J Biol Chem. 1964;239:1406-1410.
217. Cai H, Wang CC, Tsou CL. Chaperone-like activity of protein disulfide isomerase in the refolding of a protein with no disulfide bonds. J Biol Chem. 1994;269:24550-24552.
218. Wang CC, Tsou CL. Enzymes as chaperones and chaperones as enzymes. FEBS Lett. 1998;425:382-384.
219. Wilkinson B, Gilbert HF. Protein disulfide isomerase. Biochim Biophys Acta. 2004;1699:35-44.
220. Rajpal G, Schuiki I, Liu M, Volchuk A, Arvan P. Action of protein disulfide isomerase on proinsulin exit from endoplasmic reticulum of pancreatic β-cells. J Biol Chem. 2012; 287:43-47.
221. Karnik SS, Sakmar TP, Chen HB, Khorana HG. Cysteine residues 110 and 187 are essential for the formation of correct structure in bovine rhodopsin. Proc Natl Acad Sci USA. 1988;85:8459-8463.
222. Karnik SS, Khorana HG. Assembly of functional rhodopsin requires a disulfide bond between cysteine residues 110 and 187. J Biol Chem. 1990;265:17520-17524.
223. Hwa J, Reeves PJ, Klein-Seetharaman J, Davidson F, Khorana HG. Structure and function in rhodopsin: further elucidation of the role of the intradiscal cysteines, Cys-110,-185, and-187, in rhodopsin folding and function. Proc Natl Acad Sci USA. 1999;96:1932-1935.
224. McKibbin C, Toye AM, Reeves PJ, et al. Opsin stability and folding: the role of Cys185 and abnormal disulfide bond formation in the intradiscal domain. J Mol Biol. 2007;374:1309-1318.
225. Le Gouill C, Parent JL, Rola-Pleszczynski M, Stanková J. Role of the Cys90, Cys95 and Cys173 residues in the structure and function of the human platelet-activating factor receptor. FEBS Lett. 1997;402:203-208.
226. Tarnow P, Schoneberg T, Krude H, Gruters A, Biebermann H. Mutationally induced disulfide bond formation within the third extracellular loop causes melanocortin 4 receptor inactivation in patients with obesity. J Biol Chem. 2003;278:48666-48673.
227. Ayala Yáñez R, Conn PM. Protein disulfide isomerase chaperone ERP-57 decreases plasma membrane expression of the human GnRH receptor. Cell Biochem Funct. 2010;28:66-73.
228. Puig A, Gilbert HF. Protein disulfide isomerase exhibits chaperone and anti-chaperone activity in the oxidative refolding of lysozyme. J Biol Chem. 1994;269:7764-7771.
229. Tsai B, Rodighiero C, Lencer WI, Rapoport TA. Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin. Cell. 2001;104:937-948.
230. Puig A, Lyles MM, Noiva R, Gilbert HF. The role of the thiol/disulfide centers and peptide binding site in the chaperone and anti-chaperone activities of protein disulfide isomerase. J Biol Chem. 1994;269:19128-19135.
231. Huang X, Dai FF, Gaisano G, et al. The identification of novel proteins that interact with the GLP-1 receptor and restrain its activity.MolEndocrinol. 2013;27:1550-1563.
232. Ge X, Loh HH, Law PY. μ-Opioid receptor cell surface expression is regulated by its direct interaction with Ribophorin I. Mol Pharmacol. 2009;75:1307-1316.
233. Nouet S, Amzallag N, Li JM, et al. Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP. J Biol Chem. 2004;279: 28989-28997.
234. Wruck CJ, Funke-Kaiser H, Pufe T, et al. Regulation of transport of the angiotensin AT2 receptor by a novel membrane-associated Golgi protein. Arterioscler Thromb Vasc Biol. 2005;25:57-64.
235. Rodrigues-Ferreira S, Nahmias C. An ATIPical family of angiotensin II AT2 receptor-interacting proteins. Trends Endocrinol Metab. 2010;21:684-690.
236. Hicks SW, Horn TA, McCaffery JM, Zuckerman DM, Machamer CE. Golgin-160 promotes cell surface expression of the β-1 adrenergic receptor. Traffic. 2006;7:1666-1677.
237. Colley NJ, Baker EK, Stamnes MA, Zuker CS. The cyclophilin homolog NinaA is required in the secretory pathway. Cell. 1991;67:255-263.
238. Stamnes MA, Shieh BH, Chuman L, Harris GL, Zuker CS. The cyclophilin homolog NinaA is a tissue-specific integral membrane protein required for the proper synthesis of a subset of Drosophila rhodopsins. Cell. 1991;65:219-227.
239. Baker EK, Colley NJ, Zuker CS. The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin. EMBO J. 1994; 13:4886-4895.
240. Ferreira PA, Nakayama TA, Pak WL, Travis GH. Cyclophilin-related protein RanBP2 acts as chaperone for red/ green opsin. Nature. 1996;383:637-640.
241. Ferreira PA, Nakayama TA, Travis GH. Interconversion of red opsin isoforms by the cyclophilin-related chaperone protein Ran-binding protein 2. Proc Natl Acad Sci USA. 1997;94:1556-1561.
242. Chang CP, Pearse RV 2nd, O'Connell S, Rosenfeld MG. Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain. Neuron. 1993;11:1187-1195.
243. Njuki F, Nicholl CG, Howard A, et al. A new calcitoninreceptor-like sequence in rat pulmonary blood vessels. Clin Sci (Lond). 1993;85:385-388.
244. Flühmann B, Muff R, Hunziker W, Fischer JA, Born W. A human orphan calcitonin receptor-like structure. Biochem Biophys Res Commun. 1995;206:341-347.
245. McLatchie LM, Fraser NJ, Main MJ, et al. RAMPs regulate the transport and ligand specificity of the calcitoninreceptor-like receptor. Nature. 1998;393:333-339.
246. Christopoulos G, Perry KJ, Morfis M, et al. Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Mol Pharmacol. 1999;56:235-242.
247. Morfis M, Tilakaratne N, Furness SG, et al. Receptor activity-modifying proteins differentially modulate the G protein-coupling efficiency of amylin receptors. Endocrinology. 2008;149:5423-5431.
248. Bomberger JM, Parameswaran N, Hall CS, Aiyar N, Spielman WS. Novel function for receptor activity-modifying proteins (RAMPs) in post-endocytic receptor trafficking. J Biol Chem. 2005;280:9297-9307.
249. Bomberger JM, Spielman WS, Hall CS, Weinman EJ, Parameswaran N. Receptor activity-modifying protein (RAMP) isoform-specific regulation of adrenomedullin receptor trafficking by NHERF-1. J Biol Chem. 2005;280: 23926-23935.
250. Wootten D, Lindmark H, Kadmiel M, et al. Receptor activity modifying proteins (RAMPs) interact with the VPAC2 receptor and CRF1 receptors and modulate their function. Br J Pharmacol. 2013;168:822-834.
251. Christopoulos A, Christopoulos G, Morfis M, et al. Novel receptor partners and function of receptor activity-modifying proteins. J Biol Chem. 2003;278:3293-3297.
252. Harikumar KG, Simms J, Christopoulos G, Sexton PM, Miller LJ. Molecular basis of association of receptor activity-modifying protein 3 with the family B G proteincoupled secretin receptor. Biochemistry. 2009;48:11773-11785.
253. Magno AL, Ward BK, Ratajczak T. The calcium-sensing receptor: a molecular perspective. Endocr Rev. 2011;32: 3-30.
254. Bouschet T, Martin S, Henley JM. Receptor-activity-modifying proteins are required for forward trafficking of the calcium-sensing receptor to the plasma membrane. J Cell Sci. 2005;118:4709-4720.
255. Cohen SP, Haack KK, Halstead-Nussloch GE, et al. Identification of RL-TGR, a coreceptor involved in aversive chemical signaling. Proc Natl Acad Sci USA. 2010;107: 12339-12344.
256. Lu M, Echeverri F, Moyer BD. Endoplasmic reticulum retention, degradation, and aggregation of olfactory G-protein coupled receptors. Traffic. 2003;4:416-433.
257. Mombaerts P. Genes and ligands for odorant, vomeronasal and taste receptors. Nat Rev Neurosci. 2004;5:263-278.
258. Zhang Y, Chou JH, Bradley J, Bargmann CI, Zinn K. The Caenorhabditis elegans seven-transmembrane protein ODR-10 functions as an odorant receptor in mammalian cells. Proc Natl Acad Sci USA. 1997;94:12162-12167.
259. Buck L, Axel R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell. 1991;65:175-187.
260. Axel R. Scents and sensibility: a molecular logic of olfactory perception (Nobel lecture). Angew Chem Int Ed Engl. 2005;44:6110-6127.
261. Buck LB. Unraveling the sense of smell (Nobel lecture). Angew Chem Int Ed Engl. 2005;44:6128-6140.
262. Krautwurst D, Yau KW, Reed RR. Identification of ligands for olfactory receptors by functional expression of a receptor library. Cell. 1998;95:917-926.
263. Kajiya K, Inaki K, Tanaka M, Haga T, Kataoka H, Touhara K. Molecular bases of odor discrimination: reconstitution of olfactory receptors that recognize overlapping sets of odorants. J Neurosci. 2001;21:6018-6025.
264. Wellerdieck C, Oles M, Pott L, Korsching S, Gisselmann G, Hatt H. Functional expression of odorant receptors of the zebrafish Danio rerio and of the nematode C. elegans in HEK293 cells. Chem Senses. 1997;22:467-476.
265. Wetzel CH, Oles M, Wellerdieck C, Kuczkowiak M, Gisselmann G, Hatt H. Specificity and sensitivity of a human olfactory receptor functionally expressed in human embryonic kidney 293 cells and Xenopus Laevis oocytes. J Neurosci. 1999;19:7426-7433.
266. McClintock TS, Sammeta N. Trafficking prerogatives of olfactory receptors. Neuroreport. 2003;14:1547-1552.
267. Zhao H, Ivic L, Otaki JM, Hashimoto M, Mikoshiba K, Firestein S. Functional expression of a mammalian odorant receptor. Science. 1998;279:237-242.
268. Touhara K, Sengoku S, Inaki K, et al. Functional identification and reconstitution of an odorant receptor in single olfactory neurons. Proc Natl Acad Sci USA. 1999;96: 4040-4045.
269. DwyerND,Troemel ER, Sengupta P, Bargmann CI. Odorant receptor localization to olfactory cilia is mediated by ODR-4, a novel membrane-associated protein. Cell. 1998; 93:455-466.
270. Saito H, Kubota M, Roberts RW, Chi Q, Matsunami H. RTP family members induce functional expression of mammalian odorant receptors. Cell. 2004;119:679-691.
271. Von Dannecker LE, Mercadante AF, Malnic B. Ric-8B promotes functional expression of odorant receptors. Proc Natl Acad Sci USA. 2006;103:9310-9314.
272. Von Dannecker LE, Mercadante AF, Malnic B. Ric-8B, an olfactory putative GTP exchange factor, amplifies signal transduction through the olfactory-specific G-protein Gαolf. J Neurosci. 2005;25:3793-3800.
273. Zhuang H, Matsunami H. Synergism of accessory factors in functional expression of mammalian odorant receptors. J Biol Chem. 2007;282:15284-15293.
274. Gabay M, Pinter ME, Wright FA, et al. Ric-8 proteins are molecular chaperones that direct nascent G protein α subunit membrane association. Sci Signal. 2011;4:ra79.
275. Björk S, Hurt CM, Ho VK, Angelotti T. REEPs are membrane shaping adapter proteins that modulate specific G protein-coupled receptor trafficking by affecting ER cargo capacity. PLoS One. 2013;8:e76366.
276. Décaillot FM, Rozenfeld R, Gupta A, Devi LA. Cell surface targeting of μ-δ opioid receptor heterodimers by RTP4. Proc Natl Acad Sci USA. 2008;105:16045-16050.
277. Larsson MC, Domingos AI, Jones WD, Chiappe ME, Amrein H, Vosshall LB. Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron. 2004;43:703-714.
278. Neuhaus EM, Gisselmann G, Zhang W, Dooley R, Störtkuhl K, Hatt H. Odorant receptor heterodimerization in the olfactory system of Drosophila melanogaster. Nat Neurosci. 2005;8:15-17.
279. Hague C, Uberti MA, Chen Z, et al. Olfactory receptor surface expression is driven by association with the β2-adrenergic receptor. Proc Natl Acad Sci USA. 2004;101: 13672-13676.
280. Yarmolinsky DA, Zuker CS, Ryba NJ. Common sense about taste: from mammals to insects. Cell. 2009;139: 234-244.
281. Hoon MA, Adler E, Lindemeier J, Battey JF, Ryba NJ, Zuker CS. Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell. 1999;96:541-551.
282. Bachmanov AA, Li X, Reed DR, et al. Positional cloning of the mouse saccharin preference (Sac) locus. Chem Senses. 2001;26:925-933.
283. Kitagawa M, Kusakabe Y, Miura H, Ninomiya Y, Hino A. Molecular genetic identification of a candidate receptor gene for sweet taste. Biochem Biophys Res Commun. 2001;283:236-242.
284. Max M, Shanker YG, Huang L, et al. Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nat Genet. 2001;28:58-63.
285. Montmayeur JP, Liberles SD, Matsunami H, Buck LB. A candidate taste receptor gene near a sweet taste locus. Nat Neurosci. 2001;4:492-498.
286. Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS. Mammalian sweet taste receptors. Cell. 2001;106:381-390.
287. Sainz E, Korley JN, Battey JF, Sullivan SL. Identification of a novel member of the T1R family of putative taste receptors. J Neurochem. 2001;77:896-903.
288. Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E. Human receptors for sweet and umami taste. Proc Natl Acad Sci USA. 2002;99:4692-4696.
289. Nelson G, Chandrashekar J, Hoon MA, et al. An aminoacid taste receptor. Nature. 2002;416:199-202.
290. Zhao GQ, Zhang Y, Hoon MA, et al. The receptors for mammalian sweet and umami taste. Cell. 2003;115:255-266.
291. Chandrashekar J, Mueller KL,HoonMA,et al. T2Rs function as bitter taste receptors. Cell. 2000;100:703-711.
292. Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS. A novel family of mammalian taste receptors. Cell. 2000;100:693-702.
293. Matsunami H, Montmayeur JP, Buck LB. A family of candidate taste receptors in human and mouse. Nature. 2000; 404:601-604.
294. Mueller KL, Hoon MA, Erlenbach I, Chandrashekar J, Zuker CS, Ryba NJ. The receptors and coding logic for bitter taste. Nature. 2005;434:225-229.
295. Loconto J, Papes F, Chang E, et al. Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules. Cell. 2003;112:607-618.
296. Olson R, Huey-Tubman KE, Dulac C, Bjorkman PJ. Structure of a pheromone receptor-associated MHC molecule with an open and empty groove. PLoS Biol. 2005;3:e257.
297. Olson R, Dulac C, Bjorkman PJ. MHC homologs in the nervous system-they haven't lost their groove. Curr Opin Neurobiol. 2006;16:351-357.
298. Dulac C, Torello AT. Molecular detection of pheromone signals in mammals: from genes to behaviour. Nat Rev Neurosci. 2003;4:551-562.
299. Kaupmann K, Huggel K, Heid J, et al. Expression cloning of GABAB receptors uncovers similarity to metabotropic glutamate receptors. Nature. 1997;386:239-246.
300. Couve A, Filippov AK, Connolly CN, Bettler B, Brown DA, Moss SJ. Intracellular retention of recombinant GABAB receptors. J Biol Chem. 1998;273:26361-26367.
301. Jones KA, Borowsky B, Tamm JA, et al. GABAB receptors function as a heteromeric assembly of the subunits GABABR1 and GABABR2. Nature. 1998;396:674-679.
302. White JH, Wise A, Main MJ, et al. Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature. 1998;396:679-682.
303. Kuner R, Köhr G, Grünewald S, Eisenhardt G, Bach A, Kornau HC. Role of heteromer formation in GABAB receptor function. Science. 1999;283:74-77.
304. Ng GY, Clark J, Coulombe N, et al. Identification of a GABAB receptor subunit, gb2, required for functional GABAB receptor activity. J Biol Chem. 1999;274:7607-7610.
305. Martin SC, Russek SJ, Farb DH. Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1. Mol Cell Neurosci. 1999;13:180-191.
306. Margeta-MitrovicM,JanYN,Jan LY.Atrafficking checkpoint controls GABAB receptor heterodimerization. Neuron. 2000;27:97-106.
307. Calver AR, Robbins MJ, Cosio C, et al. The C-terminal domains of the GABAB receptor subunits mediate intracellular trafficking but are not required for receptor signaling. J Neurosci. 2001;21:1203-1210.
308. Margeta-Mitrovic M, Jan YN, Jan LY. Function of GB1 and GB2 subunits in G protein coupling of GABAB receptors. Proc Natl Acad Sci USA. 2001;98:14649-14654.
309. Benke D, Honer M, Michel C, Bettler B, Mohler H. γ-Aminobutyric acid type B receptor splice variant proteins GBR1a and GBR1b are both associated with GBR2 in situ and display differential regional and subcellular distribution. J Biol Chem. 1999;274:27323-27330.
310. Milligan G. G protein-coupled receptor dimerization: function and ligand pharmacology. Mol Pharmacol. 2004; 66:1-7.
311. Conn PM, Rogers DC, Stewart JM, Niedel J, Sheffield T. Conversion of a gonadotropin-releasing hormone antagonist to an agonist. Nature. 1982;296:653-655.
312. Chang W, Tu C, Cheng Z, et al. Complex formation with the type B γ-aminobutyric acid receptor affects the expression and signal transduction of the extracellular calciumsensing receptor. Studies with HEK-293 cells and neurons. J Biol Chem. 2007;282:25030-25040.
313. 2+-sensing receptor and cell differentiation in murine growth plate chondrocytes. Endocrinology. 2007;148: 4984-4992.
314. Gama L, Wilt SG, Breitwieser GE. Heterodimerization of calcium sensing receptors with metabotropic glutamate receptors in neurons. J Biol Chem. 2001;276:39053-39059.
315. Pin JP, Galvez T, Prézeau L. Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol Ther. 2003;98:325-354.
316. Hague C, Uberti MA, Chen Z, Hall RA, Minneman KP. Cell surface expression of α1D-adrenergic receptors is controlled by heterodimerization with α1B-adrenergic receptors. J Biol Chem. 2004;279:15541-15549.
317. Bush CF, Jones SV, Lyle AN, Minneman KP, Ressler KJ, Hall RA. Specificity of olfactory receptor interactions with otherGprotein-coupled receptors. J BiolChem. 2007;282: 19042-19051.
318. Xu J, Xu M, Brown T, et al. Stabilization of the μ-opioid receptor by truncated single transmembrane splice variants through a chaperone-like action. J Biol Chem. 2013;288: 21211-21227.
319. Rocheville M, Lange DC, Kumar U, Patel SC, Patel RC, Patel YC. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science. 2000;288:154-157.
320. Devi LA. Heterodimerization of G-protein-coupled receptors: pharmacology, signaling and trafficking. Trends Pharmacol Sci. 2001;22:532-537.
321. Prinster SC, Hague C, Hall RA. Heterodimerization of G protein-coupled receptors: specificity and functional significance. Pharmacol Rev. 2005;57:289-298.
322. Pin JP, Neubig R, Bouvier M, et al. International Union of Basic and Clinical Pharmacology. LXVII. Recommendations for the recognition and nomenclature of G proteincoupled receptor heteromultimers. Pharmacol Rev. 2007; 59:5-13.
323. Milligan G. G Protein-coupled receptor hetero-dimerization: contribution to pharmacology and function. Br J Pharmacol. 2009;158:5-14.
324. NoonLA, Franklin JM, King PJ, Goulding NJ, Hunyady L, Clark AJ. Failed export of the adrenocorticotrophin receptor from the endoplasmic reticulum in non-adrenal cells: evidence in support of a requirement for a specific adrenal accessory factor. J Endocrinol. 2002;174:17-25.
325. Metherell LA, Chapple JP, Cooray S, et al. Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2. Nat Genet. 2005;37:166-170.
326. Xu A, Choi KL, Wang Y, et al. Identification of novel putative membrane proteins selectively expressed during adipose conversion of 3T3-L1 cells. Biochem Biophys Res Commun. 2002;293:1161-1167.
327. Sebag JA, Hinkle PM. Melanocortin-2 receptor accessory protein MRAP forms antiparallel homodimers. Proc Natl Acad Sci USA. 2007;104:20244-20249.
328. Sebag JA, Hinkle PM. Regions of melanocortin 2 (MC2) receptor accessory protein necessary for dual topology and MC2 receptor trafficking and signaling. J Biol Chem. 2009;284:610-618.
329. Chan LF, Webb TR, Chung TT, et al. MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc Natl Acad Sci USA. 2009;106:6146-6151.
330. Kay EI, Botha R, Montgomery JM, Mountjoy KG. hMRAPa specifically alters hMC4R molecular mass and N-linked complex glycosylation in HEK293 cells. J Mol Endocrinol. 2013;50:217-227.
331. Kay EI, Botha R, Montgomery JM, Mountjoy KG. hMRAPa increases αMSH-induced hMC1R and hMC3R functional coupling and hMC4R constitutive activity. J Mol Endocrinol. 2013;50:203-215.
332. Novoselova TV, Jackson D, Campbell DC, Clark AJ, Chan LF. Melanocortin receptor accessory proteins in adrenal gland physiology and beyond. J Endocrinol. 2013;217: R1-R11.
333. Sebag JA, Hinkle PM. Opposite effects of the melanocortin-2 (MC2) receptor accessory protein MRAP on MC2 and MC5 receptor dimerization and trafficking. J Biol Chem. 2009;284:22641-22648.
334. Agulleiro MJ, Roy S, Sánchez E, Puchol S, Gallo-Payet N, Cerdá-Reverter JM. Role of melanocortin receptor accessory proteins in the function of zebrafish melanocortin receptor type 2. Mol Cell Endocrinol. 2010;320:145-152.
335. Sebag JA, Zhang C, Hinkle PM, Bradshaw AM, Cone RD. Developmental control of the melanocortin-4 receptor by MRAP2 proteins in zebrafish. Science. 2013;341:278-281.
336. Asai M, Ramachandrappa S, Joachim M, et al. Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science. 2013; 341:275-278.
337. Leclerc PC, Auger-Messier M, Lanctot PM, Escher E, Leduc R, Guillemette G. A polyaromatic caveolin-bindinglike motif in the cytoplasmic tail of the type 1 receptor for angiotensin II plays an important role in receptor trafficking and signaling. Endocrinology. 2002;143:4702-4710.
338. Binda AV, Kabbani N, Lin R, Levenson R. D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N. Mol Pharmacol. 2002;62: 507-513.
339. Achour L, Scott MG, Shirvani H, et al. CD4-CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface. Blood. 2009;113:1938-1947.
340. Satoh A, Tokunaga F, Kawamura S, Ozaki K. In situ inhibition of vesicle transport and protein processing in the dominant negative Rab1 mutant of Drosophila. J Cell Sci. 1997;110:2943-2953.
341. WuG, Zhao G, He Y. Distinct pathways for the trafficking of angiotensin II and adrenergic receptors from the endoplasmic reticulum to the cell surface: Rab1-independent transport of a G protein-coupled receptor. J Biol Chem. 2003;278:47062-47069.
342. Zhang X, Wang G, Dupré DJ, et al. Rab1 GTPase and dimerization in the cell surface expression of angiotensin II type 2 receptor. J Pharmacol Exp Ther. 2009;330:109-117.
343. Zhuang X, Adipietro KA, Datta S, Northup JK, Ray K. Rab1small GTP-binding protein regulates cell surface trafficking of the human calcium-sensing receptor. Endocrinology. 2010;151:5114-5123.
344. Hammad MM, Kuang YQ, Morse A, Dupré DJ. Rab1 interacts directly with the β2-adrenergic receptor to regulate receptor anterograde trafficking. Biol Chem. 2012; 393:541-546.
345. Shetty KM, Kurada P, O'Tousa JE. Rab6 regulation of rhodopsin transport in Drosophila. J Biol Chem. 1998; 273:20425-20430.
346. Moritz OL, Tam BM, Hurd LL, Peränen J, Deretic D, Papermaster DS. Mutant rab8 Impairs docking and fusion of rhodopsin-bearing post-Golgi membranes and causes cell death of transgenic Xenopus rods. Mol Biol Cell. 2001; 12:2341-2351.
347. 2-adrenergic receptors and differentially modulates their transport. J Biol Chem. 2010; 285:20369-20380.
348. Satoh AK, O'Tousa JE, Ozaki K, Ready DF. Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors. Development. 2005;132:1487-1497.
349. Hamelin E, Thériault C, Laroche G, Parent JL. The intracellular trafficking of the G protein-coupled receptor TPβ depends on a direct interaction with Rab11. J Biol Chem. 2005;280:36195-36205.
350. 2-adrenergic receptor through a direct interaction. Biochem J. 2009;418:163-172.
351. Li C, Fan Y, Lan TH, Lambert NA, Wu G. Rab26 modulates the cell surface transport of α2-adrenergic receptors from the Golgi. J Biol Chem. 2012;287:42784-42794.
352. Wang G, Wu G. Small GTPase regulation of GPCR anterograde trafficking. Trends Pharmacol Sci. 2012;33: 28-34.
353. Barlowe C, Orci L, Yeung T, et al. COPII: a membrane coat formed by Sec proteins that drive vesicle budding from the endoplasmic reticulum. Cell. 1994;77:895-907.
354. Rothman JE. The future of Golgi research. Mol Biol Cell. 2010;21:3776-3780.
355. Gillon AD, Latham CF, Miller EA. Vesicle-mediated ER export of proteins and lipids. Biochim Biophys Acta. 2012; 1821:1040-1049.
356. Miller EA, Barlowe C. Regulation of coat assembly-sorting things out at the ER. Curr Opin Cell Biol. 2010;22: 447-453.
357. Pucadyil TJ, Schmid SL. Conserved functions of membrane active GTPases in coated vesicle formation. Science. 2009;325:1217-1220.
358. Dong C, Zhou F, Fugetta EK, Filipeanu CM, Wu G. Endoplasmic reticulum export of adrenergic and angiotensin II receptors is differentially regulated by Sar1 GTPase. Cell Signal. 2008;20:1035-1043.
359. MadzivaMT,BirnbaumerM.Arole for ADP-ribosylation factor 6 in the processing of G-protein-coupled receptors. J Biol Chem. 2006;281:12178-12186.
360. Dong C, Zhang X, Zhou F, et al. ADP-ribosylation factors modulate the cell surface transport of G protein-coupled receptors. J Pharmacol Exp Ther. 2010;333:174-183.
361. Bailey SR, EidAH,Mitra S, Flavahan S, FlavahanNA.Rho kinase mediates cold-induced constriction of cutaneous arteries: role of α2C-adrenoceptor translocation. Circ Res. 2004;94:1367-1374.
362. Motawea HK, Jeyaraj SC, Eid AH, et al. Cyclic AMPRap1A signaling mediates cell surface translocation of microvascular smooth muscle α2C-adrenoceptors through the actin-binding protein filamin-2. Am J Physiol Cell Physiol. 2013;305:C829-C845.
363. Machamer CE, Rose JK. Vesicular stomatitis virus G proteins with altered glycosylation sites display temperaturesensitive intracellular transport and are subject to aberrant intermolecular disulfide bonding. J Biol Chem. 1988;263: 5955-5960.
364. Denning GM, Anderson MP, Amara JF, Marshall J, Smith AE, Welsh MJ. Processing of mutant cystic fibrosis transmembraneconductance regulator is temperature-sensitive. Nature. 1992;358:761-764.
365. Jaquette J, Segaloff DL. Temperature sensitivity of some mutants of the lutropin/choriogonadotropin receptor. Endocrinology. 1997;138:85-91.
366. Cheong HI, Cho HY, Park HW, Ha IS, Choi Y. Molecular genetic study of congenital nephrogenic diabetes insipidus and rescue of mutant vasopressin V2 receptor by chemical chaperones. Nephrology (Carlton). 2007;12:113-117.
367. Robben JH, Sze M, Knoers NV, Deen PM. Rescue of vasopressin V2 receptor mutants by chemical chaperones: specificity and mechanism. Mol Biol Cell. 2006;17:379-386.
368. Yu R, Chen CR, Liu X, Kodra JT. Rescue of a pathogenic mutant human glucagon receptor by pharmacological chaperones. J Mol Endocrinol. 2012;49:69-78.
369. 2-adrenergic receptors. Mol Pharmacol. 1997;51:711-720.
370. 2C-adrenoceptors from Golgi to plasma membrane in transfected human embryonic kidney 293 cells. Mol Pharmacol. 2001;60:1195-1200.
371. Mendes HF, Cheetham ME. Pharmacological manipulation of gain-of-function and dominant-negative mechadoi: nisms in rhodopsin retinitis pigmentosa. Hum Mol Genet. 2008;17:3043-3054.
372. Babcock JJ, Li M. Inside job: ligand-receptor pharmacology beneath the plasma membrane. Acta Pharmacol Sin. 2013;34:859-869.
373. Granell S, Mohammad S, Ramanagoudr-Bhojappa R, Baldini G. Obesity-linked variants of melanocortin-4 receptor are misfolded in the endoplasmic reticulum and can be rescued to the cell surface by a chemical chaperone. Mol Endocrinol. 2010;24:1805-1821.
374. Fan ZC, Tao YX. Functional characterization and pharmacological rescue of melanocortin-4 receptor mutations identified from obese patients. J Cell Mol Med. 2009;13: 3268-3282.
375. Conn PM, Leaños-Miranda A, Janovick JA. Protein origami: therapeutic rescue of misfolded gene products. Mol Interv. 2002;2:308-316.
376. Janovick JA, Maya-Nunez G, Conn PM. Rescue of hypogonadotropic hypogonadism-causing and manufactured GnRH receptor mutants by a specific protein-folding template: misrouted proteins as a novel disease etiology and therapeutic target. J Clin Endocrinol Metab. 2002;87: 3255-3262.
377. Lester HA, Miwa JM, Srinivasan R. Psychiatric drugs bind to classical targets within early exocytotic pathways: therapeutic effects. Biol Psychiatry. 2012;72:907-915.
378. Ulloa-Aguirre A, Janovick JA, Brothers SP, Conn PM. Pharmacologic rescue of conformationally-defective proteins: implications for the treatment of human disease. Traffic. 2004;5:821-837.
379. Bernier V, Lagacé M, Bichet DG, Bouvier M. Pharmacological chaperones: potential treatment for conformational diseases. Trends Endocrinol Metab. 2004;15:222-228.
380. Castro-Fernández C, Maya-Núñez G, Conn PM. Beyond the signal sequence: protein routing in health and disease. Endocr Rev. 2005;26:479-503.
381. Sun Y, Breydo L, Makarava N, Yang Q, Bocharova OV, Baskakov IV. Site-specific conformational studies of prion protein (PrP) amyloid fibrils revealed two cooperative folding domains within amyloid structure. J Biol Chem. 2007; 282:9090-9097.
382. Stefani M. Protein misfolding and aggregation: new examples in medicine and biology of the dark side of the protein world. Biochim Biophys Acta. 2004;1739:5-25.
383. Pande A, Pande J, Asherie N, et al. Crystal cataracts: human genetic cataract caused by protein crystallization. Proc Natl Acad Sci USA. 2001;98:6116-6120.
384. Zhang XM, Wang XT, Yue H, et al. Organic solutes rescue the functional defect in δ F508 cystic fibrosis transmembrane conductance regulator. J Biol Chem. 2003;278: 51232-51242.
385. Amaral MD. Therapy through chaperones: sense or antisense? Cystic fibrosis as a model disease. J Inherit Metab Dis. 2006;29:477-487.
386. Loo TW, Clarke DM. Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators. J Biol Chem. 1997;272:709-712.
387. Wang QY, Manicassamy B, Yu X, Dolmer K, Gettins PG, Rong L. Characterization of the LDL-A module mutants of Tva, the subgroup A Rous sarcoma virus receptor, and the implications in protein folding. Protein Sci. 2002;11: 2596-2605.
388. Zhou Z, Gong Q, January CT. Correction of defective protein trafficking of a mutant HERG potassium channel in human long QT syndrome. Pharmacological and temperature effects. J Biol Chem. 1999;274:31123-31126.
389. Benedek GB, Pande J, Thurston GM, Clark JI. Theoretical and experimental basis for the inhibition of cataract. Prog Retin Eye Res. 1999;18:391-402.
390. Heiser V, Scherzinger E, Boeddrich A, et al. Inhibition of huntingtin fibrillogenesis by specific antibodies and small molecules: implications for Huntington's disease therapy. Proc Natl Acad Sci USA. 2000;97:6739-6744.
391. Permanne B, Adessi C, Saborio GP, et al. Reduction of amyloid load and cerebral damage in a transgenic mouse model of Alzheimer's disease by treatment with a β-sheet breaker peptide. FASEB J. 2002;16:860-862.
392. Soto C, Kascsak RJ, Saborío GP, et al. Reversion of prion protein conformational changes by synthetic β-sheet breaker peptides. Lancet. 2000;355:192-197.
393. Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci. 2005; 6:11-22.
394. Foster BA, Coffey HA, Morin MJ, Rastinejad F. Pharmacological rescue of mutant p53 conformation and function. Science. 1999;286:2507-2510.
395. Burrows JA, Willis LK, Perlmutter DH. Chemical chaperones mediate increased secretion of mutant α 1-antitrypsin (α 1-AT) Z: a potential pharmacological strategy for prevention of liver injury and emphysema in α 1-AT deficiency. Proc Natl Acad Sci USA. 2000;97:1796-1801.
396. Bottomley SP. The structural diversity in α1-antitrypsin misfolding. EMBO Rep. 2011;12:983-984.
397. Fan JQ, Ishii S, Asano N, Suzuki Y. Accelerated transport and maturation of lysosomal α-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor. Nat Med. 1999;5: 112-115.
398. Sawkar AR, Cheng WC, Beutler E, Wong CH, Balch WE, Kelly JW. Chemical chaperones increase the cellular activity of N370S β-glucosidase: a therapeutic strategy for Gaucher disease. Proc Natl Acad Sci USA. 2002;99:15428-15433.
399. Parenti G, Zuppaldi A, Gabriela Pittis M, et al. Pharmacological enhancement of mutated α-glucosidase activity in fibroblasts from patients with Pompe disease. Mol Ther. 2007;15:508-514.
400. Clark NE, Metcalf MC, Best D, Fleet GW, Garman SC. Pharmacological chaperones for human α-N-acetylgalactosaminidase. Proc Natl Acad Sci USA. 2012;109:17400-17405.
401. Kuryatov A, Luo J, Cooper J, Lindstrom J. Nicotine acts as a pharmacological chaperone to up-regulate human α4β2 acetylcholine receptors. Mol Pharmacol. 2005;68:1839-1851.
402. Srinivasan R, Richards CI, Xiao C, et al. Pharmacological chaperoning of nicotinic acetylcholine receptors reduces the endoplasmic reticulum stress response. Mol Pharmacol. 2012;81:759-769.
403. Feldhammer M, Durand S, Pshezhetsky AV. Protein misfolding as an underlying molecular defect in mucopolysaccharidosis III type C. PLoS One. 2009;4:e7434.
404. Jorge-Finnigan A, Brasil S, Underhaug J, et al. Pharmacological chaperones as a potential therapeutic option in methylmalonic aciduria cblB type. HumMol Genet. 2013; 22:3680-3689.
405. Martinez A, Calvo AC, Teigen K, Pey AL. Rescuing proteins of low kinetic stability by chaperones and natural ligands phenylketonuria, a case study. Prog Mol Biol Transl Sci. 2008;83:89-134.
406. Santos-Sierra S, Kirchmair J, Perna AM, et al. Novel pharmacological chaperones that correct phenylketonuria in mice. Hum Mol Genet. 2012;21:1877-1887.
407. Dawson G, Schroeder C, Dawson PE. Palmitoyl:protein thioesterase (PPT1) inhibitors can act as pharmacological chaperones in infantile Batten disease. Biochem Biophys Res Commun. 2010;395:66-69.
408. Loo TW, Clarke DM. Chemical and pharmacological chaperones as new therapeutic agents. Expert Rev Mol Med. 2007;9:1-18.
409. Gavrin LK, Denny RA, Saiah E. Small molecules that target protein misfolding. J Med Chem. 2012;55:10823-10843.
410. Van Goor F, Hadida S, Grootenhuis PD, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci USA. 2011;108:18843-18848.
411. Clancy JP, Rowe SM, Accurso FJ, et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax. 2012;67:12-18.
412. Kresge N. Pharmacological chaperones show. Am Soc Biochem Mol Biol Today. 2004;3:10-11.
413. Hunter PJ. Receptor redemption: skirting gene therapy to correct genetic defects. Scientist. 2004;18:30.
414. Engel J, Emons G, Pinski J, Schally AV. AEZS-108: a targeted cytotoxic analog of LHRH for the treatment of cancers positive for LHRH receptors. Expert Opin Investig Drugs. 2012;21:891-899.
415. Kovacs M, Schally AV, Nagy A, Koppan M, Groot K. Recovery of pituitary function after treatment with a targeted cytotoxic analog of luteinizing hormone-releasing hormone. Proc Natl Acad Sci USA. 1997;94:1420-1425.
416. Comaru-Schally AM, Brannan W, Schally AV, Colcolough M, Monga M. Efficacy and safety of luteinizing hormone-releasing hormone antagonist cetrorelix in the treatment of symptomatic benign prostatic hyperplasia. J Clin Endocrinol Metab. 1998;83:3826-3831.
417. Limonta P, Moretti RM, Marelli MM, Dondi D, Parenti M, Motta M. The luteinizing hormone-releasing hormone receptor in human prostate cancer cells: messenger ribonucleic acid expression, molecular size, and signal transduction pathway. Endocrinology. 1999;140:5250-5256.
418. Keller G, Schally AV, Gaiser T, et al. Human malignant melanomas express receptors for luteinizing hormone releasing hormone allowing targeted therapy with cytotoxic luteinizing hormone releasing hormone analogue. Cancer Res. 2005;65:5857-5863.
419. Limonta P, Montagnani Marelli M, Mai S, Motta M, Martini L, Moretti RM. GnRH receptors in cancer: from cell biology to novel targeted therapeutic strategies. Endocr Rev. 2012;33:784-811.
420. Waldstreicher J, Seminara SB, Jameson JL, et al. The genetic and clinical heterogeneity of gonadotropin-releasing hormone deficiency in the human. J Clin Endocrinol Metab. 1996;81:4388-4395.
421. Seminara SB, Beranova M, Oliveira LM, Martin KA, Crowley WF Jr, Hall JE. Successful use of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction and pregnancy in a patient with GnRH receptor mutations. J Clin Endocrinol Metab. 2000;85:556-562.
422. Stewart MD, Deng JM, Stewart CA, et al. Mice harboring Gnrhr E90K, a mutation that causes protein misfolding and hypogonadotropic hypogonadism in humans, exhibit testis size reduction and ovulation failure. Mol Endocrinol. 2012;26:1847-1856.
423. Janovick JA, Stewart MD, Jacob D, et al. Restoration of testis function in hypogonadotropic hypogonadal mice harboring a misfolded GnRHR mutant by pharmacoperone drug therapy. Proc Natl Acad Sci USA. 2013;110: 21030-21035.
424. Janovick JA, Patny A, Mosley R, et al. Molecular mechanism of action of pharmacoperone rescue of misrouted GPCR mutants: the GnRH receptor. Mol Endocrinol. 2009;23:157-168.
425. Janovick JA, Conn PM. Salt bridge integrates GPCR activation with protein trafficking. Proc Natl Acad Sci USA. 2010;107:4454-4458.
426. Janovick JA, Pogozheva ID, Mosberg HI, Conn PM. Salt bridges overlapping the gonadotropin-releasing hormone receptor agonist binding site reveal a coincidence detector for G protein-coupled receptor activation. J Pharmacol Exp Ther. 2011;338:430-442.
427. Knollman PE, Janovick JA, Brothers SP,ConnPM.Parallel regulation of membrane trafficking and dominant-negative effects by misrouted gonadotropin-releasing hormone receptor mutants. J Biol Chem. 2005;280:24506-24514.
428. Janovick JA, Knollman PE, Brothers SP, Ayala-Yáñez R, Aziz AS, Conn PM. Regulation of G protein-coupled receptor trafficking by inefficient plasma membrane expression: molecular basis of an evolved strategy. J Biol Chem. 2006;281:8417-8425.
429. Soderlund D, Canto P, de la Chesnaye E, Ulloa-Aguirre A, Méndez JP. A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor gene. Clin Endocrinol (Oxf). 2001;54: 493-498.
430. Conn PM, Janovick JA. Drug development and the cellular quality control system. Trends Pharmacol Sci. 2009;30: 228-233.
431. Conn PM, Ulloa-Aguirre A. Trafficking of G-protein-coupled receptors to the plasma membrane: insights for pharmacoperone drugs. Trends Endocrinol Metab. 2010;21: 190-197.
432. Janovick JA, Goulet M, Bush E, Greer J, Wettlaufer DG, Conn PM. Structure-activity relations of successful pharmacologic chaperones for rescue of naturally occurring and manufactured mutants of the gonadotropin-releasing hormone receptor. J Pharmacol Exp Ther. 2003;305:608-614.
433. Janovick JA, Brothers SP, Cornea A, et al. Refolding of misfolded mutant GPCR: post-translational pharmacoperone action in vitro. Mol Cell Endocrinol. 2007;272: 77-85.
434. Morello JP, Salahpour A, Laperrière A, et al. Pharmacodoi: logical chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest. 2000;105:887-895.
435. Rosenthal W, Seibold A, Antaramian A, et al. Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus. Nature. 1992;359:233-235.
436. Moeller HB, Rittig S, Fenton RA. Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment. Endocr Rev. 2013; 34:278-301.
437. Oueslati M, Hermosilla R, Schönenberger E, et al. Rescue of a nephrogenic diabetes insipidus-causing vasopressin V2 receptor mutant by cell-penetrating peptides. J Biol Chem. 2007;282:20676-20685.
438. Wüller S, Wiesner B, Löffler A, et al. Pharmacochaperones post-translationally enhance cell surface expression by increasing conformational stability of wild-type and mutant vasopressin V2 receptors. J Biol Chem. 2004;279:47254-47263.
439. Bernier V, LagacéM,LonerganM,Arthus MF, Bichet DG, Bouvier M. Functional rescue of the constitutively internalized V2 vasopressin receptor mutant R137H by the pharmacological chaperone action of SR49059. Mol Endocrinol. 2004;18:2074-2084.
440. Robben JH, Sze M, Knoers NV, Deen PM. Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones: relevance to therapy of nephrogenic diabetes insipidus. Am J Physiol Renal Physiol. 2007;292: F253-F260.
441. Jean-Alphonse F, Perkovska S, Frantz MC, et al. Biased agonist pharmacochaperones of the AVP V2 receptor may treat congenital nephrogenic diabetes insipidus. J Am Soc Nephrol. 2009;20:2190-2203.
442. Robben JH, Kortenoeven ML, Sze M, et al. Intracellular activation of vasopressin V2 receptor mutants in nephrogenic diabetes insipidus by nonpeptide agonists. Proc Natl Acad Sci USA. 2009;106:12195-12200.
443. Los EL, Deen PM, Robben JH. Potential of nonpeptide (ant)agonists to rescue vasopressin V2 receptor mutants for the treatment of X-linked nephrogenic diabetes insipidus. J Neuroendocrinol. 2010;22:393-399.
444. Bernier V, Morello JP, Zarruk A, et al. Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus. J AmSoc Nephrol. 2006;17:232-243.
445. Welch WJ, Howard M. Antagonists to the rescue. J Clin Invest. 2000;105:853-854.
446. Li T, Sandberg MA, Pawlyk BS, et al. Effect of vitamin A supplementation on rhodopsin mutants threonine-17 → methionine and proline-347 → serine in transgenic mice and in cell cultures. Proc Natl Acad Sci USA. 1998;95: 11933-11938.
447. Tam BM, Moritz OL. Dark rearing rescues P23H rhodopsin-induced retinal degeneration in a transgenic Xenopus laevis model of retinitis pigmentosa: a chromophore-dependent mechanism characterized by production of N-terminally truncated mutant rhodopsin. J Neurosci. 2007;27: 9043-9053.
448. Saliba RS, Munro PM, Luthert PJ, Cheetham ME. The cellular fate of mutant rhodopsin: quality control, degradation and aggresome formation. J Cell Sci. 2002;115: 2907-2918.
449. Noorwez SM, Kuksa V, Imanishi Y, et al. Pharmacological chaperone-mediated in vivo folding and stabilization of the P23H-opsin mutant associated with autosomal dominant retinitis pigmentosa. J Biol Chem. 2003;278:14442-14450.
450. Noorwez SM, Malhotra R, McDowell JH, Smith KA, Krebs MP, Kaushal S. Retinoids assist the cellular folding of the autosomal dominant retinitis pigmentosa opsin mutant P23H. J Biol Chem. 2004;279:16278-16284.
451. Krebs MP, Holden DC, Joshi P, Clark CL 3rd, Lee AH, Kaushal S. Molecular mechanisms of rhodopsin retinitis pigmentosa and the efficacy of pharmacological rescue. J Mol Biol. 2010;395:1063-1078.
452. Tao YX. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology. Endocr Rev. 2010;31: 506-543.
453. Wang ZQ, Tao YX. Functional studies on twenty novel naturally occurring melanocortin-4 receptor mutations. Biochim Biophys Acta. 2011;1812:1190-1199.
454. René P, Le Gouill C, Pogozheva ID, et al. Pharmacological chaperones restore function to MC4 Rmutants responsible for severe early-onset obesity. J Pharmacol Exp Ther. 2010;335:520-532.
455. Ward NA, Hirst S, Williams J, Findlay JB. Pharmacological chaperones increase the cell-surface expression of intracellularly retained mutants of the melanocortin 4 receptor with unique rescuing efficacy profiles. Biochem Soc Trans. 2012;40:717-720.
456. Tao YX, Segaloff DL. Functional analyses of melanocortin-4 receptor mutations identified from patients with binge eating disorder and nonobese or obese subjects. J Clin Endocrinol Metab. 2005;90:5632-5638.
457. Lee YS, Poh LK, Kek BL, Loke KY. The role of melanocortin 3 receptor gene in childhood obesity. Diabetes. 2007;56:2622-2630.
458. Mencarelli M, Walker GE, Maestrini S, et al. Sporadic mutations in melanocortin receptor 3 in morbid obese individuals. Eur J Hum Genet. 2008;16:581-586.
459. Zhou C, Dhall D, Nissen NN, Chen CR, Yu R. Homozygous P86S mutation of the human glucagon receptor is associated with hyperglucagonemia, α cell hyperplasia, and islet cell tumor. Pancreas. 2009;38:941-946.
460. Labrecque P, Roy SJ, Frechette L, Iorio-Morin C, Gallant MA, Parent JL. Inverse agonist and pharmacochaperone properties of MK-0524 on the prostanoid DP1 receptor. PLoS One. 2013;8:e65767.
461. Huang Y, Breitwieser GE. Rescue of calcium-sensing receptor mutants by allosteric modulators reveals a conformational checkpoint in receptor biogenesis. J Biol Chem. 2007;282:9517-9525.
462. White E, McKenna J, Cavanaugh A, Breitwieser GE. Pharmacochaperone-mediated rescue of calcium-sensing receptor loss-of-function mutants. Mol Endocrinol. 2009;23: 1115-1123.
463. Rus R, Haag C, Bumke-Vogt C, et al. Novel inactivating mutations of the calcium-sensing receptor: the calcimimetic NPS R-568 improves signal transduction of mutant receptors. J Clin Endocrinol Metab. 2008;93:4797-4803.
464. Nakamura A, Hotsubo T, Kobayashi K, Mochizuki H, Ishizu K, Tajima T. Loss-of-function and gain-of-function mutations of calcium-sensing receptor: functional analysis and the effect of allosteric modulators NPS R-568 and NPS 2143. J Clin Endocrinol Metab. 2013;98:E1692-E1701.
465. Leach K, Wen A, Cook AE, Sexton PM, Conigrave AD, Christopoulos A. Impact of clinically relevant mutations on the pharmacoregulation and signaling bias of the calcium-sensing receptor by positive and negative allosteric modulators. Endocrinology. 2013;154:1105-1116.
466. Newton CL, Whay AM, McArdle CA, et al. Rescue of expression and signaling of human luteinizing hormone G protein-coupled receptor mutants with an allosterically binding small-molecule agonist. Proc Natl Acad Sci USA. 2011;108:7172-7176.
467. Hakalahti AE, Khan H, Vierimaa MM, et al. β-Adrenergic agonists mediate enhancement of β1-adrenergic receptor N-terminal cleavage and stabilization in vivo and in vitro. Mol Pharmacol. 2013;83:129-141.
468. Chaipatikul V, Erickson-Herbrandson LJ, Loh HH, Law PY. Rescuing the traffic-deficient mutants of rat μ-opioid receptors with hydrophobic ligands. Mol Pharmacol. 2003;64:32-41.
469. Chen Y, Chen C, Wang Y, Liu-Chen LY. Ligands regulate cell surface level of the human κ opioid receptor by activation-induced down-regulation and pharmacological chaperone-mediated enhancement: differential effects of nonpeptide and peptide agonists. J Pharmacol Exp Ther. 2006;319:765-775.
470. WannemacherKM,Yadav PN, Howells RD.Aselect set of opioid ligands induce up-regulation by promoting the maturation and stability of the rat κ-opioid receptor in human embryonic kidney 293 cells. J Pharmacol Exp Ther. 2007; 323:614-625.
471. Petäjä-Repo UE, Hogue M, Bhalla S, Laperrière A, Morello JP, Bouvier M. Ligands act as pharmacological chaperones and increase the efficiency of δ opioid receptor maturation. EMBO J. 2002;21:1628-1637.
472. Hawtin SR. Pharmacological chaperone activity of SR49059 to functionally recover misfolded mutations of the vasopressin V1a receptor. J Biol Chem. 2006;281: 14604-14614.
473. Robert J, Auzan C, Ventura MA, Clauser E. Mechanisms of cell-surface rerouting of an endoplasmic reticulum-retained mutant of the vasopressin V1b/V3 receptor by a pharmacological chaperone. J Biol Chem. 2005;280: 42198-42206.
474. Fortin JP, Dziadulewicz EK, Gera L, Marceau F. A nonpeptide antagonist reveals a highly glycosylated state of the rabbit kinin B1 receptor. Mol Pharmacol. 2006;69:1146-1157.
475. Málaga-Diéguez L, Yang Q, Bauer J, Pankevych H, Freissmuth M, Nanoff C. Pharmacochaperoning of the A1 adenosine receptor is contingent on the endoplasmic reticulum. Mol Pharmacol. 2010;77:940-952.
476. Yasuda D, Okuno T, Yokomizo T, et al. Helix 8 of leukotriene B4 type-2 receptor is required for the folding to pass the quality control in the endoplasmic reticulum. FASEB J. 2009;23:1470-1481.
477. Van Craenenbroeck K, Clark SD, Cox MJ, Oak JN, Liu F, Van Tol HH. Folding efficiency is rate-limiting in dopamine D4 receptor biogenesis. J Biol Chem. 2005;280: 19350-19357.
478. Hetz C, Martinon F, Rodriguez D, Glimcher LH. The unfolded protein response: integrating stress signals through the stress sensor IRE1α. Physiol Rev. 2011;91:1219-1243.
479. Lin JH, Lavail MM. Misfolded proteins and retinal dystrophies. Adv Exp Med Biol. 2010;664:115-121.
480. Fonseca SG, Gromada J, Urano F. Endoplasmic reticulum stress and pancreatic β-cell death. Trends Endocrinol Metab. 2011;22:266-274.
481. ConnPM,Janovick JA. Pharmacoperone identification for therapeutic rescue of misfolded mutant proteins. Front Endocrinol (Lausanne). 2011;2:pii: 00006.
482. Janovick JA, Park BS, Conn PM. Therapeutic rescue of misfolded mutants: validation of primary high throughput screens for identification of pharmacoperone drugs. PLoS One. 2011;6:e22784.
483. Smithson DC, Janovick JA, Conn PM. Therapeutic rescue of misfolded/mistrafficked mutants: automation-friendly high-throughput assays for identification of pharmacoperone drugs of GPCRs. Methods Enzymol. 2013;521:3-16.
484. Conn PM, Smith E, Hodder P, Janovick JA, Smithson DC. High-throughput screen for pharmacoperones of the vasopressin type 2 receptor. J Biomol Screen. 2013;18:930-937.
485. Noorwez SM, Ostrov DA, McDowell JH, Krebs MP, Kaushal S. A high-throughput screening method for smallmolecule pharmacologic chaperones of misfolded rhodopsin. Invest Ophthalmol Vis Sci. 2008;49:3224-3230.
486. Dryja TP,McGeeTL,HahnLB, et al. Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. N Engl J Med. 1990;323:1302-1307.
487. Dryja TP, McGee TL, Reichel E, et al. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature. 1990;343:364-366.
488. Morimura H, Saindelle-Ribeaudeau F, Berson EL, Dryja TP. Mutations in RGR, encoding a light-sensitive opsin homologue, in patients with retinitis pigmentosa. Nat Genet. 1999;23:393-394.
489. Weitz CJ, Miyake Y, Shinzato K, et al. Human tritanopia associated with two amino acid substitutions in the bluesensitive opsin. Am J Hum Genet. 1992;50:498-507.
490. Nathans J. In the eye of the beholder: visual pigments and inherited variation in human vision. Cell. 1994;78:357-360.
491. Piao X, Hill RS, Bodell A, et al. G protein-coupled receptor-dependent development of human frontal cortex. Science. 2004;303:2033-2036.
492. Jin Z, Tietjen I, Bu L, et al. Disease-associated mutations affect GPR56 protein trafficking and cell surface expression. Hum Mol Genet. 2007;16:1972-1985.
493. Jin Z, Luo R, Piao X. GPR56 and its related diseases. Prog Mol Biol Transl Sci. 2009;89:1-13.
494. ColeLW,Sidis Y, Zhang C, et al. Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum. J Clin Endocrinol Metab. 2008;93: 3551-3559.
495. Martin C, Balasubramanian R, Dwyer AA, et al. The role of the prokineticin 2 pathway in human reproduction: evdoi: idence from the study of human and murine gene mutations. Endocr Rev. 2011;32:225-246.
496. de Roux N, Young J, Misrahi M, et al. A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. N Engl J Med. 1997;337:1597-1602.
497. Layman LC, Cohen DP, Jin M, et al. Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. Nat Genet. 1998;18:14-15.
498. Wajnrajch MP, Gertner JM, Harbison MD, Chua SC Jr, Leibel RL. Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat Genet. 1996;12: 88-90.
499. Martari M, Salvatori R. Diseases associated with growth hormone-releasing hormone receptor (GHRHR) mutations. Prog Mol Biol Transl Sci. 2009;88:57-84.
500. Collu R, Tang J, Castagné J, et al. A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene. J Clin Endocrinol Metab. 1997;82:1561-1565.
501. Seminara SB, Messager S, Chatzidaki EE, et al. TheGPR54 gene as a regulator of puberty. N Engl J Med. 2003;349: 1614-1627.
502. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA. 2003;100:10972-10976.
503. Biebermann H, Grüters A, Schöneberg T, Gudermann T. Congenital hypothyroidism caused by mutations in the thyrotropin-receptor gene. N Engl J Med. 1997;336: 1390-1391.
504. Kremer H, Kraaij R, Toledo SP, et al. Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet. 1995; 9:160-164.
505. Laue L,WuSM, Kudo M, et al.Anonsense mutation of the human luteinizing hormone receptor gene in Leydig cell hypoplasia. Hum Mol Genet. 1995;4:1429-1433.
506. Aittomäki K, Lucena JL, Pakarinen P, et al. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. 1995;82: 959-968.
507. Topaloglu AK, Reimann F, Guclu M, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction. Nat Genet. 2009;41:354-358.
508. Gorlov IP, Kamat A, Bogatcheva NV, et al. Mutations of the GREAT gene cause cryptorchidism. Hum Mol Genet. 2002;11:2309-2318.
509. Pollak MR, Brown EM, Chou YH, et al. Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Cell. 1993;75:1297-1303.
510. Zhang P, Jobert AS, Couvineau A, Silve C. A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia. J Clin Endocrinol Metab. 1998; 83:3365-3368.
511. Jobert AS, Zhang P, Couvineau A, et al. Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. J Clin Invest. 1998;102:34-40.
512. Couvineau A, Wouters V, Bertrand G, et al. PTHR1 mutations associated with Ollier disease result in receptor loss of function. Hum Mol Genet. 2008;17:2766-2775.
513. Valverde P, Healy E, Jackson I, Rees JL, Thody AJ. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat Genet. 1995;11:328-330.
514. Clark AJ, McLoughlin L, Grossman A. Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Lancet. 1993;341:461-462.
515. Tsigos C, Arai K, Hung W, Chrousos GP. Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene. J Clin Invest. 1993;92:2458-2461.
516. Lee YS, Poh LK, Loke KY. A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity. J Clin Endocrinol Metab. 2002;87:1423-1426.
517. Vaisse C, Clement K, Guy-Grand B, Froguel P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet. 1998;20:113-114.
518. Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O'Rahilly S. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet. 1998;20:111-112.
519. Hinney A, Schmidt A, Nottebom K, et al. Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans. J Clin Endocrinol Metab. 1999;84:1483-1486.
520. Hinney A, Volckmar AL, Knoll N. Melanocortin-4 receptor in energy homeostasis and obesity pathogenesis. Prog Mol Biol Transl Sci. 2013;114:147-191.
521. Liu R, Paxton WA, Choe S, et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996;86: 367-377.
522. Samson M, Libert F, Doranz BJ, et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996;382: 722-725.
523. Hernandez PA, Gorlin RJ, Lukens JN, et al. Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet. 2003;34:70-74.
524. + individuals with a structural variant of the chemokine receptor CX3CR1. Science. 2000;287: 2274-2277.
525. Tournamille C, Le Van Kim C, Gane P, et al. Arg89Cys substitution results in very low membrane expression of the Duffy antigen/receptor for chemokines in Fy(x) individuals. Blood. 1998;92:2147-2156.
526. Tokuyama Y, Matsui K, Egashira T, Nozaki O, Ishizuka T, Kanatsuka A. Five missense mutations in glucagon-like peptide 1 receptor gene in Japanese population. Diabetes Res Clin Pract. 2004;66:63-69.
527. Hager J, Hansen L, Vaisse C, et al. A missense mutation in the glucagon receptor gene is associated with non-insulindependent diabetes mellitus. Nat Genet. 1995;9:299-304.
528. Wang HJ, Geller F, Dempfle A, et al. Ghrelin receptor gene: identification of several sequence variants in extremely obese children and adolescents, healthy normal-weight and underweight students, and children with short normal stature. J Clin Endocrinol Metab. 2004;89:157-162.
529. Pantel J, Legendre M, Cabrol S, et al. Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature. J Clin Invest. 2006;116:760-768.
530. Mo XL, Wei HK, Peng J, Tao YX. Free fatty acid receptor GPR120 and pathogenesis of obesity and type 2 diabetes mellitus. Prog Mol Biol Transl Sci. 2013;114:251-276.
531. Vettor R, Granzotto M, De Stefani D, et al. Loss-of-function mutation of the GPR 40 gene associates with abnormal stimulated insulin secretion by acting on intracellular calcium mobilization. J Clin Endocrinol Metab. 2008;93: 3541-3550.
532. Puffenberger EG, Hosoda K, Washington SS, et al. A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. Cell. 1994;79:1257-1266.
533. Thompson MD, Comings DE, Abu-Ghazalah R, et al. Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity. Am J Med GenetB Neuropsychiatr Genet. 2004;129B:69-75.
534. Hirata T, Kakizuka A, Ushikubi F, Fuse I, Okuma M, Narumiya S. Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder. J Clin Invest. 1994;94:1662-1667.
535. Hollopeter G, Jantzen HM, Vincent D, et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature. 2001;409:202-207.
536. Kan Z, Jaiswal BS, Stinson J, et al. Diverse somatic mutation patterns and pathway alterations in human cancers. Nature. 2010;466:869-873.
537. Gwinn MR, Sharma A, De Nardin E. Single nucleotide polymorphisms of the N-formyl peptide receptor in localized juvenile periodontitis. J Periodontol. 1999;70:1194-1201.
538. Nakayama J, Fu YH, Clark AM, et al. A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures. Ann Neurol. 2002;52:654-657.
539. Weston MD, Luijendijk MW, Humphrey KD, Möller C, Kimberling WJ. Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II. Am J Hum Genet. 2004;74:357-366.
540. Vervoort VS, Beachem MA, Edwards PS, et al. AGTR2 mutations in X-linked mental retardation. Science. 2002; 296:2401-2403.
541. MaRZ, Gao J, Meeker ND,et al. Identification of Bphs, an autoimmune disease locus, as histamine receptor H1. Science. 2002;297:620-623.
542. Arehart E, Stitham J, Asselbergs FW, et al. Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor mutation: potential implications for cyclooxygenase-2 inhibition. Circ Res. 2008;102:986-993.
543. Karsak M, Cohen-Solal M, Freudenberg J, et al. Cannabinoid receptor type 2 gene is associated with human osteoporosis. Hum Mol Genet. 2005;14:3389-3396.
544. Bassi MT, Schiaffino MV, Renieri A, et al. Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome. Nat Genet. 1995;10:13-19.
545. Kazius J, Wurdinger K, van Iterson M, Kok J, Bäck T, Ijzerman AP. GPCR NaVa database: natural variants in human G protein-coupled receptors. Hum Mutat. 2008; 29:39-44.
546. Leaños-Miranda A, Ulloa-Aguirre A, Janovick JA, Conn PM. In vitro coexpression and pharmacological rescue of mutant gonadotropin-releasing hormone receptors causing hypogonadotropic hypogonadism in humans expressing compound heterozygous alleles. J Clin Endocrinol Metab. 2005;90:3001-3008.