Mutations in G protein-coupled receptors that impact receptor trafficking and reproductive function

Molecular and Cellular Endocrinology

Volumn 382, Issue 1, 2014, Pages 411-423

  Ulloa Aguirre, Alfredo ^a,b   Zariñán, Teresa ^c   Dias, James A ^d   Conn, P Michael ^b,e,f  

^a INSTITUTO NACIONAL DE SALUD PÚBLICA   (Mexico)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^c Research Unit in Reproductive Medicine   (Mexico)

^d STATE UNIVERSITY OF NEW YORK   (United States)

^e OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^f OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

G protein coupled receptors; Gonadotropin receptors; Gonadotropin releasing hormone receptor; Hipogonadism; Intracellular trafficking; Pharmacological chaperones

Indexed keywords

FOLLITROPIN RECEPTOR; G PROTEIN COUPLED RECEPTOR; GONADORELIN RECEPTOR; LUTEINIZING HORMONE RECEPTOR; MUTANT PROTEIN;

ARTICLE; CELL MEMBRANE; DRUG TARGETING; ENDOPLASMIC RETICULUM; GENE MUTATION; HUMAN; HYPERGONADOTROPIC HYPOGONADISM; HYPOGONADOTROPIC HYPOGONADISM; HYPOPHYSIS GONAD SYSTEM; LOSS OF FUNCTION MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN STRUCTURE; PROTEIN TRANSPORT; REPRODUCTION; SENSORY STIMULATION; SIGNAL TRANSDUCTION;

G PROTEIN-COUPLED RECEPTORS; GONADOTROPIN RECEPTORS; GONADOTROPIN-RELEASING HORMONE RECEPTOR; HIPOGONADISM; INTRACELLULAR TRAFFICKING; PHARMACOLOGICAL CHAPERONES;

ANIMALS; HUMANS; HYPOGONADISM; MUTATION; PROTEIN TRANSPORT; RECEPTORS, G-PROTEIN-COUPLED; REPRODUCTION;

EID: 84888305386     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2013.06.024     Document Type: Article

References (163)

1. Achrekar S.K., Modi D.N., Meherji P.K., Patel Z.M., Mahale S.D. Follicle stimulating hormone receptor gene variants in women with primary and secondary amenorrhea. J. Assist. Reprod. Genet. 2010, 27:317-326.
2. Aittomaki K., Lucena J.L., Pakarinen P., Sistonen P., Tapanainen J., Gromoll J., Kaskikari R., Sankila E.M., Lehvaslaiho H., Engel A.R., Nieschlag E., Huhtaniemi I., de la Chapelle A. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 1995, 82:959-968.
3. Aittomaki K., Herva R., Stenman U.H., Juntunen K., Ylostalo P., Hovatta O., de la Chapelle A. Clinical features of primary ovarian failure caused by a point mutation in the follicle-stimulating hormone receptor gene. J. Clin. Endocrinol. Metab. 1996, 81:3722-3726.
4. Allen L.A., Achermann J.C., Pakarinen P., Kotlar T.J., Huhtaniemi I.T., Jameson J.L., Cheetham T.D., Ball S.G. A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: clinical and molecular characteristics. Hum. Reprod. 2003, 18:251-256.
5. Angelotti T., Daunt D., Shcherbakova O.G., Kobilka B., Hurt C.M. Regulation of G-protein coupled receptor traffic by an evolutionary conserved hydrophobic signal. Traffic 2010, 11:560-578.
6. Arakawa T., Ejima D., Kita Y., Tsumoto K. Small molecule pharmacological chaperones: from thermodynamic stabilization to pharmaceutical drugs. Biochim. Biophys. Acta 2006, 1764:1677-1687.
7. Arora K.K., Chung H.O., Catt K.J. Influence of a species-specific extracellular amino acid on expression and function of the human gonadotropin-releasing hormone receptor. Mol. Endocrinol. 1999, 13:890-896.
8. Ascoli M., Fanelli F., Segaloff D.L. The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr. Rev. 2002, 23:141-174.
9. Beau I., Touraine P., Meduri G., Gougeon A., Desroches A., Matuchansky C., Milgrom E., Kuttenn F., Misrahi M. A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor. J. Clin. Invest. 1998, 102:1352-1359.
10. Beranova M., Oliveira L.M., Bedecarrats G.Y., Schipani E., Vallejo M., Ammini A.C., Quintos J.B., Hall J.E., Martin K.A., Hayes F.J., Pitteloud N., Kaiser U.B., Crowley W.F., Seminara S.B. Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 2001, 86:1580-1588.
11. Bernier V., Bichet D.G., Bouvier M. Pharmacological chaperone action on G-protein-coupled receptors. Curr. Opin. Pharmacol. 2004, 4:528-533.
12. Bernier V., Lagace M., Bichet D.G., Bouvier M. Pharmacological chaperones: potential treatment for conformational diseases. Trends Endocrinol. Metab. 2004, 15:222-228.
13. Bernier V., Morello J.P., Zarruk A., Debrand N., Salahpour A., Lonergan M., Arthus M.F., Laperriere A., Brouard R., Bouvier M., Bichet D.G. Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus. J. Am. Soc. Nephrol. 2006, 17:232-243.
14. Blanpain C., Wittamer V., Vanderwinden J.M., Boom A., Renneboog B., Lee B., Le Poul E., El Asmar L., Govaerts C., Vassart G., Doms R.W., Parmentier M. Palmitoylation of CCR5 is critical for receptor trafficking and efficient activation of intracellular signaling pathways. J. Biol. Chem. 2001, 276:23795-23804.
15. Blomenrohr M., Heding A., Sellar R., Leurs R., Bogerd J., Eidne K.A., Willars G.B. Pivotal role for the cytoplasmic carboxyl-terminal tail of a nonmammalian gonadotropin-releasing hormone receptor in cell surface expression, ligand binding, and receptor phosphorylation and internalization. Mol. Pharmacol. 1999, 56:1229-1237.
16. Bogerd J. Ligand-selective determinants in gonadotropin receptors. Mol. Cell. Endocrinol. 2007, 260-262:144-152.
17. Breitwieser G.E. G protein-coupled receptor oligomerization: implications for G protein activation and cell signaling. Circ. Res. 2004, 94:17-27.
18. Broadley S.A., Hartl F.U. The role of molecular chaperones in human misfolding diseases. FEBS Lett. 2009, 583:2647-2653.
19. Brooks D.A. Introduction: molecular chaperones of the ER: their role in protein folding and genetic disease. Semin. Cell Dev. Biol. 1999, 10:441-442.
20. Brothers S.P., Cornea A., Janovick J.A., Conn P.M. 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.
21. Calebiro D., de Filippis T., Lucchi S., Covino C., Panigone S., Beck-Peccoz P., Dunlap D., Persani L. Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance. Hum. Mol. Genet. 2005, 14:2991-3002.
22. Castro-Fernandez C., Maya-Nunez G., Conn P.M. Beyond the signal sequence: protein routing in health and disease. Endocr. Rev. 2005, 26:479-503.
23. Chevet E., Cameron P.H., Pelletier M.F., Thomas D.Y., Bergeron J.J. The endoplasmic reticulum: integration of protein folding, quality control, signaling and degradation. Curr. Opin. Struct. Biol. 2001, 11:120-124.
24. Conn P.M., Crowley W.F. Gonadotropin-releasing hormone and its analogs. Annu. Rev. Med. 1994, 45:391-405.
25. Conn P.M., Janovick J.A. Drug development and the cellular quality control system. Trends Pharmacol. Sci. 2009, 30:228-233.
26. Conn P.M., Janovick J.A. Pharmacoperone identification for therapeutic rescue of misfolded mutant proteins. Front. Endocrinol. (Lausanne) 2011, 2. pii: 00006.
27. Conn P.M., Ulloa-Aguirre A. Trafficking of G-protein-coupled receptors to the plasma membrane: insights for pharmacoperone drugs. Trends Endocrinol. Metab. 2010, 21:190-197.
28. Conn P.M., Ulloa-Aguirre A. Pharmacological chaperones for misfolded gonadotropin-releasing hormone receptors. Adv. Pharmacol. 2011, 62C:109-141.
29. Conn P.M., Knollman P.E., Brothers S.P., Janovick J.A. Protein folding as posttranslational regulation: evolution of a mechanism for controlled plasma membrane expression of a G protein-coupled receptor. Mol. Endocrinol. 2006, 20:3035-3041.
30. Conn P.M., Ulloa-Aguirre A., Ito J., Janovick J.A. G protein-coupled receptor trafficking in health and disease: lessons learned to prepare for therapeutic mutant rescue in vivo. Pharmacol. Rev. 2007, 59:225-250.
31. Davis D., Liu X., Segaloff D.L. 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.
32. Dias J.A., Cohen B.D., Lindau-Shepard B., Nechamen C.A., Peterson A.J., Schmidt A. Molecular, structural, and cellular biology of follitropin and follitropin receptor. Vitam. Horm. 2002, 64:249-322.
33. Doherty E., Pakarinen P., Tiitinen A., Kiilavuori A., Huhtaniemi I., Forrest S., Aittomaki K. A novel mutation in the FSH receptor inhibiting signal transduction and causing primary ovarian failure. J. Clin. Endocrinol. Metab. 2002, 87:1151-1155.
34. Dupakuntla M., Pathak B., Roy B.S., Mahale S.D. Extracellular loop 2 in the FSH receptor is crucial for ligand mediated receptor activation. Mol. Cell. Endocrinol. 2012, 362:60-68.
35. Duvernay M.T., Zhou F., Wu G. A conserved motif for the transport of G protein-coupled receptors from the endoplasmic reticulum to the cell surface. J. Biol. Chem. 2004, 279:30741-30750.
36. Estrada L.D., Soto C. Inhibition of protein misfolding and aggregation by small rationally-designed peptides. Curr. Pharm. Des. 2006, 12:2557-2567.
37. Estrada L.D., Soto C. Disrupting beta-amyloid aggregation for Alzheimer disease treatment. Curr. Top. Med. Chem. 2007, 7:115-126.
38. Fan Q.R., Hendrickson W.A. Structure of human follicle-stimulating hormone in complex with its receptor. Nature 2005, 433:269-277.
39. Fan Q.R., Hendrickson W.A. Assembly and structural characterization of an authentic complex between human follicle stimulating hormone and a hormone-binding ectodomain of its receptor. Mol. Cell. Endocrinol. 2007, 260-262:73-82.
40. Fan T., Varghese G., Nguyen T., Tse R., O'Dowd B.F., George S.R. A role for the distal carboxyl tails in generating the novel pharmacology and G protein activation profile of mu and delta opioid receptor hetero-oligomers. J. Biol. Chem. 2005, 280:38478-38488.
41. Francou B., Bouligand J., Voican A., Amazit L., Trabado S., Fagart J., Meduri G., Brailly-Tabard S., Chanson P., Lecomte P., Guiochon-Mantel A., Young J. Normosmic congenital hypogonadotropic hypogonadism due to TAC3/TACR3 mutations: characterization of neuroendocrine phenotypes and novel mutations. PLoS ONE 2011, 6:e25614.
42. Fredriksson R., Lagerstrom M.C., Lundin L.G., Schioth H.B. 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.
43. Fukushima Y., Saitoh T., Anai M., Ogihara T., Inukai K., Funaki M., Sakoda H., Onishi Y., Ono H., Fujishiro M., Ishikawa T., Takata K., Nagai R., Omata M., Asano T. Palmitoylation of the canine histamine H2 receptor occurs at Cys(305) and is important for cell surface targeting. Biochim. Biophys. Acta 2001, 1539:181-191.
44. Gething M.J. Role and regulation of the ER chaperone BiP. Semin. Cell Dev. Biol. 1999, 10:465-472.
45. Gianetti E., Hall J.E., Au M.G., Kaiser U.B., Quinton R., Stewart J.A., Metzger D.L., Pitteloud N., Mericq V., Merino P.M., Levitsky L.L., Izatt L., Lang-Muritano M., Fujimoto V.Y., Dluhy R.G., Chase M.L., Crowley W.F., Plummer L., Seminara S.B. When genetic load does not correlate with phenotypic spectrum: lessons from the GnRH receptor (GNRHR). J. Clin. Endocrinol. Metab. 2012, 97:E1798-E1807.
46. Gromoll J., Simoni M., Nieschlag E. An activating mutation of the follicle-stimulating hormone receptor autonomously sustains spermatogenesis in a hypophysectomized man. J. Clin. Endocrinol. Metab. 1996, 81:1367-1370.
47. Gromoll J., Simoni M., Nordhoff V., Behre H.M., De Geyter C., Nieschlag E. Functional and clinical consequences of mutations in the FSH receptor. Mol. Cell. Endocrinol. 1996, 125:177-182.
48. Gromoll J., Schulz A., Borta H., Gudermann T., Teerds K.J., Greschniok A., Nieschlag E., Seif F.J. Homozygous mutation within the conserved Ala-Phe-Asn-Glu-Thr motif of exon 7 of the LH receptor causes male pseudohermaphroditism. Eur. J. Endocrinol. 2002, 147:597-608.
49. Guan R., Feng X., Wu X., Zhang M., Zhang X., Hebert T.E., Segaloff D.L. Bioluminescence resonance energy transfer studies reveal constitutive dimerization of the human lutropin receptor and a lack of correlation between receptor activation and the propensity for dimerization. J. Biol. Chem. 2009, 284:7483-7494.
50. Guan R., Wu X., Feng X., Zhang M., Hebert T.E., Segaloff D.L. Structural determinants underlying constitutive dimerization of unoccupied human follitropin receptors. Cell. Signal. 2010, 22:247-256.
51. Hammarstrom P., Wiseman R.L., Powers E.T., Kelly J.W. Prevention of transthyretin amyloid disease by changing protein misfolding energetics. Science 2003, 299:713-716.
52. Hartl F.U., Hayer-Hartl M. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 2002, 295:1852-1858.
53. Hartl F.U., Hayer-Hartl M. Converging concepts of protein folding in vitro and in vivo. Nat. Struct. Mol. Biol. 2009, 16:574-581.
54. Hartl F.U., Bracher A., Hayer-Hartl M. Molecular chaperones in protein folding and proteostasis. Nature 2011, 475:324-332.
55. Hebert T.E., Moffett S., Morello J.P., Loisel T.P., Bichet D.G., Barret C., Bouvier M. A peptide derived from a beta2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J. Biol. Chem. 1996, 271:16384-16392.
56. Heding A., Vrecl M., Bogerd J., McGregor A., Sellar R., Taylor P.L., Eidne K.A. Gonadotropin-releasing hormone receptors with intracellular carboxyl-terminal tails undergo acute desensitization of total inositol phosphate production and exhibit accelerated internalization kinetics. J. Biol. Chem. 1998, 273:11472-11477.
57. Helenius A., Aebi M. Roles of N-linked glycans in the endoplasmic reticulum. Annu. Rev. Biochem. 2004, 73:1019-1049.
58. Huhtaniemi I., Alevizaki M. Mutations along the hypothalamic-pituitary-gonadal axis affecting male reproduction. Reprod. Biomed. Online 2007, 15:622-632.
59. Huhtaniemi I.T., Themmen A.P. Mutations in human gonadotropin and gonadotropin-receptor genes. Endocrine 2005, 26:207-217.
60. Huhtaniemi I.T., Clayton R.N., Catt K.J. Gonadotropin binding and Leydig cell activation in the rat testis in vivo. Endocrinology 1982, 111:982-987.
61. Hunzicker-Dunn M., Maizels E.T. FSH signaling pathways in immature granulosa cells that regulate target gene expression: branching out from protein kinase A. Cell. Signal. 2006, 18:1351-1359.
62. Hutt D.M., Powers E.T., Balch W.E. The proteostasis boundary in misfolding diseases of membrane traffic. FEBS Lett. 2009, 583:2639-2646.
63. Ishii S., Chang H.H., Kawasaki K., Yasuda K., Wu H.L., Garman S.C., Fan J.Q. Mutant alpha-galactosidase A enzymes identified in Fabry disease patients with residual enzyme activity: biochemical characterization and restoration of normal intracellular processing by 1-deoxygalactonojirimycin. Biochem. J. 2007, 406:285-295.
64. Janovick J.A., Conn P.M. Salt bridge integrates GPCR activation with protein trafficking. Proc. Natl. Acad. Sci. USA 2010, 107:4454-4458.
65. Janovick J.A., Maya-Nunez G., Conn P.M. 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.
66. Janovick J.A., Goulet M., Bush E., Greer J., Wettlaufer D.G., Conn P.M. 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.
67. Janovick J.A., Ulloa-Aguirre A., Conn P.M. Evolved regulation of gonadotropin-releasing hormone receptor cell surface expression. Endocrine 2003, 22:317-327.
68. Janovick J.A., Knollman P.E., Brothers S.P., Ayala-Yanez R., Aziz A.S., Conn P.M. 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.
69. Janovick J.A., Maya-Nunez G., Ulloa-Aguirre A., Huhtaniemi I.T., Dias J.A., Verbost P., Conn P.M. Increased plasma membrane expression of human follicle-stimulating hormone receptor by a small molecule thienopyr(im)idine. Mol. Cell. Endocrinol. 2009, 298:84-88.
70. Janovick J.A., Patny A., Mosley R., Goulet M.T., Altman M.D., Rush T.S., Cornea A., Conn P.M. Molecular mechanism of action of pharmacoperone rescue of misrouted GPCR mutants: the GnRH receptor. Mol. Endocrinol. 2009, 23:157-168.
71. Jardon-Valadez E., Ulloa-Aguirre A., Pineiro A. Modeling and molecular dynamics simulation of the human gonadotropin-releasing hormone receptor in a lipid bilayer. J. Phys. Chem. B 2008, 112:10704-10713.
72. Jardon-Valadez E., Aguilar-Rojas A., Maya-Nunez G., Leanos-Miranda A., Pineiro A., Conn P.M., Ulloa-Aguirre A. Conformational effects of Lys191 in the human GnRH receptor: mutagenesis and molecular dynamics simulations studies. J. Endocrinol. 2009, 201:297-307.
73. Jiang X., Liu H., Chen X., Chen P.H., Fischer D., Sriraman V., Yu H.N., Arkinstall S., He X. Structure of follicle-stimulating hormone in complex with the entire ectodomain of its receptor. Proc. Natl. Acad. Sci. USA 2012, 109:12491-12496.
74. Karges B., Karges W., de Roux N. Clinical and molecular genetics of the human GnRH receptor. Hum. Reprod. Update 2003, 9:523-530.
75. Kawate N., Menon K.M. Palmitoylation of luteinizing hormone/human choriogonadotropin receptors in transfected cells. Abolition of palmitoylation by mutation of Cys-621 and Cys-622 residues in the cytoplasmic tail increases ligand-induced internalization of the receptor. J. Biol. Chem. 1994, 269:30651-30658.
76. Klausner R.D., Sitia R. Protein degradation in the endoplasmic reticulum. Cell 1990, 62:611-614.
77. Kotlar T.J., Young R.H., Albanese C., Crowley W.F., Scully R.E., Jameson J.L. A mutation in the follicle-stimulating hormone receptor occurs frequently in human ovarian sex cord tumors. J. Clin. Endocrinol. Metab. 1997, 82:1020-1026.
78. Kremer H., Kraaij R., Toledo S.P., Post M., Fridman J.B., Hayashida C.Y., van Reen M., Milgrom E., Ropers H.H., Mariman E., et al. Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat. Genet. 1995, 9:160-164.
79. Lagerstrom M.C., Schioth H.B. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat. Rev. Drug Discov. 2008, 7:339-357.
80. Latronico A.C., Anasti J., Arnhold I.J., Rapaport R., Mendonca B.B., Bloise W., Castro M., Tsigos C., Chrousos G.P. Brief report: testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone-receptor gene. N. Engl. J. Med. 1996, 334:507-512.
81. Latronico A.C., Chai Y., Arnhold I.J., Liu X., Mendonca B.B., Segaloff D.L. A homozygous microdeletion in helix 7 of the luteinizing hormone receptor associated with familial testicular and ovarian resistance is due to both decreased cell surface expression and impaired effector activation by the cell surface receptor. Mol. Endocrinol. 1998, 12:442-450.
82. Laue L.L., Wu S.M., Kudo M., Bourdony C.J., Cutler G.B., Hsueh A.J., Chan W.Y. Compound heterozygous mutations of the luteinizing hormone receptor gene in Leydig cell hypoplasia. Mol. Endocrinol. 1996, 10:987-997.
83. Layman L.C., Porto A.L., Xie J., da Motta L.A., da Motta L.D., Weiser W., Sluss P.M. FSH beta gene mutations in a female with partial breast development and a male sibling with normal puberty and azoospermia. J. Clin. Endocrinol. Metab. 2002, 87:3702-3707.
84. Le Gouill C., Parent J.L., Caron C.A., Gaudreau R., Volkov L., Rola-Pleszczynski M., Stankova J. Selective modulation of wild type receptor functions by mutants of G-protein-coupled receptors. J. Biol. Chem. 1999, 274:12548-12554.
85. Leanos-Miranda A., Janovick J.A., Conn P.M. Receptor-misrouting: an unexpectedly prevalent and rescuable etiology in gonadotropin-releasing hormone receptor-mediated hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 2002, 87:4825-4828.
86. Leanos-Miranda A., Ulloa-Aguirre A., Ji T.H., Janovick J.A., Conn P.M. Dominant-negative action of disease-causing gonadotropin-releasing hormone receptor (GnRHR) mutants: a trait that potentially coevolved with decreased plasma membrane expression of GnRHR in humans. J. Clin. Endocrinol. Metab. 2003, 88:3360-3367.
87. Leanos-Miranda A., Ulloa-Aguirre A., Janovick J.A., Conn P.M. 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.
88. Lee S.P., O'Dowd B.F., Rajaram R.D., Nguyen T., George S.R. D2 dopamine receptor homodimerization is mediated by multiple sites of interaction, including an intermolecular interaction involving transmembrane domain 4. Biochemistry 2003, 42:11023-11031.
89. Lin X., Janovick J.A., Brothers S., Blomenrohr M., Bogerd J., Conn P.M. 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.
90. Lindstedt G., Nystrom E., Matthews C., Ernest I., Janson P.O., Chatterjee K. Follitropin (FSH) deficiency in an infertile male due to FSHbeta gene mutation. A syndrome of normal puberty and virilization but underdeveloped testicles with azoospermia, low FSH but high lutropin and normal serum testosterone concentrations. Clin. Chem. Lab. Med. 1998, 36:663-665.
91. Loo T.W., Clarke D.M. Chemical and pharmacological chaperones as new therapeutic agents. Expert Rev. Mol. Med. 2007, 9:1-18.
92. Marshall F.H., Jones K.A., Kaupmann K., Bettler B. GABAB receptors - the first 7TM heterodimers. Trends Pharmacol. Sci. 1999, 20:396-399.
93. Martens J.W., Verhoef-Post M., Abelin N., Ezabella M., Toledo S.P., Brunner H.G., Themmen A.P. A homozygous mutation in the luteinizing hormone receptor causes partial Leydig cell hypoplasia: correlation between receptor activity and phenotype. Mol. Endocrinol. 1998, 12:775-784.
94. Martens J.W., Lumbroso S., Verhoef-Post M., Georget V., Richter-Unruh A., Szarras-Czapnik M., Romer T.E., Brunner H.G., Themmen A.P., Sultan C. Mutant luteinizing hormone receptors in a compound heterozygous patient with complete Leydig cell hypoplasia: abnormal processing causes signaling deficiency. J. Clin. Endocrinol. Metab. 2002, 87:2506-2513.
95. Maya-Nunez G., Janovick J.A., Ulloa-Aguirre A., Soderlund D., Conn P.M., Mendez J.P. Molecular basis of hypogonadotropic hypogonadism: restoration of mutant (E(90)K) GnRH receptor function by a deletion at a distant site. J. Clin. Endocrinol. Metab. 2002, 87:2144-2149.
96. Maya-Nunez G., Janovick J.A., Aguilar-Rojas A., Jardon-Valadez E., Leanos-Miranda A., Zarinan T., Ulloa-Aguirre A., Conn P.M. Biochemical mechanism of pathogenesis of human gonadotropin-releasing hormone receptor mutants Thr104Ile and Tyr108Cys associated with familial hypogonadotropic hypogonadism. Mol. Cell. Endocrinol. 2011, 337:16-23.
97. McArdle C.A., Davidson J.S., Willars G.B. The tail of the gonadotrophin-releasing hormone receptor: desensitization at, and distal to, G protein-coupled receptors. Mol. Cell. Endocrinol. 1999, 151:129-136.
98. Meduri G., Touraine P., Beau I., Lahuna O., Desroches A., Vacher-Lavenu M.C., Kuttenn F., Misrahi M. Delayed puberty and primary amenorrhea associated with a novel mutation of the human follicle-stimulating hormone receptor: clinical, histological, and molecular studies. J. Clin. Endocrinol. Metab. 2003, 88:3491-3498.
99. Millar R.P. GnRH II and type II GnRH receptors. Trends Endocrinol. Metab. 2003, 14:35-43.
100. Millar R.P., Lu Z.L., Pawson A.J., Flanagan C.A., Morgan K., Maudsley S.R. Gonadotropin-releasing hormone receptors. Endocr. Rev. 2004, 25:235-275.
101. Mizrachi D., Segaloff D.L. Intracellularly located misfolded glycoprotein hormone receptors associate with different chaperone proteins than their cognate wild-type receptors. Mol. Endocrinol. 2004, 18:1768-1777.
102. Monnier C., Dode C., Fabre L., Teixeira L., Labesse G., Pin J.P., Hardelin J.P., Rondard P. PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity. Hum. Mol. Genet. 2009, 18:75-81.
103. Morello J.P., Petaja-Repo U.E., Bichet D.G., Bouvier M. Pharmacological chaperones: a new twist on receptor folding. Trends Pharmacol. Sci. 2000, 21:466-469.
104. Morello J.P., Salahpour A., Laperriere A., Bernier V., Arthus M.F., Lonergan M., Petaja-Repo U., Angers S., Morin D., Bichet D.G., Bouvier M. Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J. Clin. Invest. 2000, 105:887-895.
105. Mueller S., Jaeschke H., Gunther R., Paschke R. The hinge region: an important receptor component for GPHR function. Trends Endocrinol. Metab. 2009, 21:111-122.
106. Munshi U.M., Clouser C.L., Peegel H., Menon K.M. Evidence that palmitoylation of carboxyl terminus cysteine residues of the human luteinizing hormone receptor regulates postendocytic processing. Mol. Endocrinol. 2005, 19:749-758.
107. Musnier A., Heitzler D., Boulo T., Tesseraud S., Durand G., Lecureuil C., Guillou H., Poupon A., Reiter E., Crepieux P. Developmental regulation of p70 S6 kinase by a G protein-coupled receptor dynamically modelized in primary cells. Cell. Mol. Life Sci. 2009, 66:3487-3503.
108. Nakamura Y., Maekawa R., Yamagata Y., Tamura I., Sugino N. A novel mutation in exon8 of the follicle-stimulating hormone receptor in a woman with primary amenorrhea. Gynecol. Endocrinol. 2008, 24:708-712.
109. Nakamura M., Yasuda D., Hirota N., Shimizu T. Specific ligands as pharmacological chaperones: the transport of misfolded G-protein coupled receptors to the cell surface. IUBMB Life 2010, 62:453-459.
110. Nechamen C.A., Dias J.A. Point mutations in follitropin receptor result in ER retention. Mol. Cell. Endocrinol. 2003, 201:123-131.
111. Nechamen C.A., Thomas R.M., Dias J.A. APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling complex. Mol. Cell. Endocrinol. 2007, 260-262:93-99.
112. Newton C.L., Whay A.M., McArdle C.A., Zhang M., van Koppen C.J., van de Lagemaat R., Segaloff D.L., Millar R.P. 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.
113. Ng G.Y., O'Dowd B.F., Lee S.P., Chung H.T., Brann M.R., Seeman P., George S.R. Dopamine D2 receptor dimers and receptor-blocking peptides. Biochem. Biophys. Res. Commun. 1996, 227:200-204.
114. Nimri R., Lebenthal Y., Lazar L., Chevrier L., Phillip M., Bar M., Hernandez-Mora E., de Roux N., Gat-Yablonski G. A novel loss-of-function mutation in GPR54/KISS1R leads to hypogonadotropic hypogonadism in a highly consanguineous family. J. Clin. Endocrinol. Metab. 2011, 96:E536-45.
115. Okamoto T., Nishimoto I. Detection of G protein-activator regions in M4 subtype muscarinic, cholinergic, and alpha 2-adrenergic receptors based upon characteristics in primary structure. J. Biol. Chem. 1992, 267:8342-8346.
116. Overington J.P., Al-Lazikani B., Hopkins A.L. How many drug targets are there?. Nat. Rev. Drug Discov. 2006, 5:993-996.
117. Percherancier Y., Planchenault T., Valenzuela-Fernandez A., Virelizier J.L., Arenzana-Seisdedos F., Bachelerie F. Palmitoylation-dependent control of degradation, life span, and membrane expression of the CCR5 receptor. J. Biol. Chem. 2001, 276:31936-31944.
118. Rannikko A., Pakarinen P., Manna P.R., Beau I., Misrahi M., Aittomaki K., Huhtaniemi I. Functional characterization of the human FSH receptor with an inactivating Ala189Val mutation. Mol. Hum. Reprod. 2002, 8:311-317.
119. Resh, M.D., 2006. Palmitoylation of ligands, receptors, and intracellular signaling molecules. Sci. STKE 2006, re14.
120. Richter-Unruh A., Martens J.W., Verhoef-Post M., Wessels H.T., Kors W.A., Sinnecker G.H., Boehmer A., Drop S.L., Toledo S.P., Brunner H.G., Themmen A.P. Leydig cell hypoplasia: cases with new mutations, new polymorphisms and cases without mutations in the luteinizing hormone receptor gene. Clin. Endocrinol. (Oxf.) 2002, 56:103-112.
121. Richter-Unruh A., Verhoef-Post M., Malak S., Homoki J., Hauffa B.P., Themmen A.P. Leydig cell hypoplasia: absent luteinizing hormone receptor cell surface expression caused by a novel homozygous mutation in the extracellular domain. J. Clin. Endocrinol. Metab. 2004, 89:5161-5167.
122. Robben J.H., Sze M., Knoers N.V., Deen P.M. Rescue of vasopressin V2 receptor mutants by chemical chaperones: specificity and mechanism. Mol. Biol. Cell 2006, 17:379-386.
123. Ron D., Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 2007, 8:519-529.
124. Rozell T.G., Wang H., Liu X., Segaloff D.L. Intracellular retention of mutant gonadotropin receptors results in loss of hormone binding activity of the follitropin rreceptor but not the lutropin/choriogonadotropin receptor. Mol. Endocrinol. 1995, 9:1727-1736.
125. Rozell T.G., Davis D.P., Chai Y., Segaloff D.L. Association of gonadotropin receptor precursors with the protein folding chaperone calnexin. Endocrinology 1998, 139:1588-1593.
126. Sampedro J.G., Uribe S. Trehalose-enzyme interactions result in structure stabilization and activity inhibition. The role of viscosity. Mol. Cell. Biochem. 2004, 256-257:319-327.
127. Schlyer S., Horuk R. I want a new drug: G-protein-coupled receptors in drug development. Drug Discov. Today 2006, 11:481-493.
128. Schubert U., Anton L.C., Gibbs J., Norbury C.C., Yewdell J.W., Bennink J.R. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 2000, 404:770-774.
129. Schulz A., Schoneberg T., Paschke R., Schultz G., Gudermann T. Role of the third intracellular loop for the activation of gonadotropin receptors. Mol. Endocrinol. 1999, 13:181-190.
130. Sigurdsson E.M., Permanne B., Soto C., Wisniewski T., Frangione B. In vivo reversal of amyloid-beta lesions in rat brain. J. Neuropathol. Exp. Neurol. 2000, 59:11-17.
131. Simoni M., Gromoll J., Nieschlag E. The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr. Rev. 1997, 18:739-773.
132. Smithson D.C., Janovick J.A., Conn P.M. Therapeutic rescue of misfolded/mistrafficked mutants: automation-friendly high-throughput assays for identification of pharmacoperone drugs of GPCRs. Methods Enzymol. 2013, 521:3-16.
133. Soderlund D., Canto P., de la Chesnaye E., Ulloa-Aguirre A., Mendez J.P. A novel homozygous mutation in the second transmembrane domain of the gonadotrophin releasing hormone receptor gene. Clin. Endocrinol. (Oxf.) 2001, 54:493-498.
134. Song Y.S., Ji I., Beauchamp J., Isaacs N.W., Ji T.H. Hormone interactions to Leu-rich repeats in the gonadotropin receptors. II. Analysis of Leu-rich repeat 4 of human luteinizing hormone/chorionic gonadotropin receptor. J. Biol. Chem. 2001, 276:3436-3442.
135. Soto C. Protein misfolding and disease; protein refolding and therapy. FEBS Lett. 2001, 498:204-207.
136. Stewart M.D., Deng J.M., Stewart C.A., Mullen R.D., Wang Y., Lopez S., Serna M.K., Huang C.C., Janovick J.A., Pask A.J., Schwartz R.J., Conn P.M., Behringer R.R. 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.
137. Szidonya L., Cserzo M., Hunyady L. Dimerization and oligomerization of G-protein-coupled receptors: debated structures with established and emerging functions. J. Endocrinol. 2008, 196:435-453.
138. Tanaka K., Nagayama Y., Nishihara E., Namba H., Yamashita S., Niwa M. Palmitoylation of human thyrotropin receptor: slower intracellular trafficking of the palmitoylation-defective mutant. Endocrinology 1998, 139:803-806.
139. Tao Y.X., Johnson N.B., Segaloff D.L. Constitutive and agonist-dependent self-association of the cell surface human lutropin receptor. J. Biol. Chem. 2004, 279:5904-5914.
140. Tapanainen J.S., Aittomaki K., Min J., Vaskivuo T., Huhtaniemi I.T. Men homozygous for an inactivating mutation of the follicle-stimulating hormone (FSH) receptor gene present variable suppression of spermatogenesis and fertility. Nat. Genet. 1997, 15:205-206.
141. Thomas R.M., Nechamen C.A., Mazurkiewicz J.E., Muda M., Palmer S., Dias J.A. Follice-stimulating hormone receptor forms oligomers and shows evidence of carboxyl-terminal proteolytic processing. Endocrinology 2007, 148:1987-1995.
142. Timossi C., Ortiz-Elizondo C., Pineda D.B., Dias J.A., Conn P.M., Ulloa-Aguirre A. Functional significance of the BBXXB motif reversed present in the cytoplasmic domains of the human follicle-stimulating hormone receptor. Mol. Cell. Endocrinol. 2004, 223:17-26.
143. Toledo S.P., Brunner H.G., Kraaij R., Post M., Dahia P.L., Hayashida C.Y., Kremer H.T.A.P. An inactivating mutation of the luteinizing hormone receptor causes amenorrhea in a 46, XX female. J. Clin. Endocrinol. Metab. 1996, 81:3850-3854.
144. Touraine P., Beau I., Gougeon A., Meduri G., Desroches A., Pichard C., Detoeuf M., Paniel B., Prieur M., Zorn J.R., Milgrom E., Kuttenn F., Misrahi M. New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. Mol. Endocrinol. 1999, 13:1844-1854.
145. Tranchant T., Durand G., Gauthier C., Crepieux P., Ulloa-Aguirre A., Royere D., Reiter E. Preferential beta-arrestin signalling at low receptor density revealed by functional characterization of the human FSH receptor A189 V mutation. Mol. Cell. Endocrinol. 2011, 331:109-118.
146. Ulloa-Aguirre A., Conn P.M. G protein-coupled receptors and the G protein family. Handbook of Physiology-Endocrinology: Section 7, Cellular Endocrinology 1998, 87-141. Oxford University Press, New York, USA. P.M. Conn (Ed.).
147. Ulloa-Aguirre A., Conn P.M. Targeting of G protein-coupled receptors to the plasma membrane in health and disease. Front. Biosci. 2009, 14:973-994.
148. Ulloa-Aguirre A., Conn P.M. Pharmacoperones: a new therapeutic approach for diseases caused by misfolded G protein-coupled receptors. Recent Pat. Endocr. Metab. Immune Drug Discov. 2011, 5:13-24.
149. Ulloa-Aguirre A., Timossi C. Structure-function relationship of follicle-stimulating hormone and its receptor. Hum. Reprod. Update 1998, 4:260-283.
150. Ulloa-Aguirre A., Timossi C. Biochemical and functional aspects of gonadotrophin-releasing hormone and gonadotrophins. Reprod. Biomed. Online 2000, 1:48-62.
151. Ulloa-Aguirre A., Janovick J.A., Leanos-Miranda A., Conn P.M. Misrouted cell surface receptors as a novel disease aetiology and potential therapeutic target: the case of hypogonadotropic hypogonadism due to gonadotropin-releasing hormone resistance. Exp. Opin. Ther. Targets 2003, 7:175-185.
152. Ulloa-Aguirre A., Janovick J.A., Leanos-Miranda A., Conn P.M. Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism. Hum. Reprod. Update 2004, 10:177-192.
153. Ulloa-Aguirre A., Janovick J.A., Miranda A.L., Conn P.M. G-protein-coupled receptor trafficking: understanding the chemical basis of health and disease. ACS Chem. Biol. 2006, 1:631-638.
154. Ulloa-Aguirre A., Crepieux P., Poupon A., Maurel M.C., Reiter E. Novel pathways in gonadotropin receptor signaling and biased agonism. Rev. Endocr. Metab. Disord. 2011, 12:259-274.
155. Uribe A., Zarinan T., Perez-Solis M.A., Gutierrez-Sagal R., Jardon-Valadez E., Pineiro A., Dias J.A., Ulloa-Aguirre A. Functional and structural roles of conserved cysteine residues in the carboxyl-terminal domain of the follicle-stimulating hormone receptor in human embryonic kidney 293 cells. Biol. Reprod. 2008, 78:869-882.
156. van Straten N.C., Schoonus-Gerritsma G.G., van Someren R.G., Draaijer J., Adang A.E., Timmers C.M., Hanssen R.G., van Boeckel C.A. The first orally active low molecular weight agonists for the LH receptor: thienopyr(im)idines with therapeutic potential for ovulation induction. ChemBioChem 2002, 3:1023-1026.
157. Vaskivuo T.E., Aittomaki K., Anttonen M., Ruokonen A., Herva R., Osawa Y., Heikinheimo M., Huhtaniemi I., Tapanainen J.S. Effects of follicle-stimulating hormone (FSH) and human chorionic gonadotropin in individuals with an inactivating mutation of the FSH receptor. Fertil. Steril. 2002, 78:108-113.
158. Vassart G., Pardo L., Costagliola S. A molecular dissection of the glycoprotein hormone receptors. Trends Biochem. Sci. 2004, 29:119-126.
159. Weekes M.P., Antrobus R., Talbot S., Hor S., Simecek N., Smith D.L., Bloor S., Randow F., Lehner P.J. Proteomic plasma membrane profiling reveals an essential role for gp96 in the cell surface expression of LDLR family members, including the LDL receptor and LRP6. J. Proteome Res. 2012, 11:1475-1484.
160. Werner E.D., Brodsky J.L., McCracken A.A. Proteasome-dependent endoplasmic reticulum-associated protein degradation: an unconventional route to a familiar fate. Proc. Natl. Acad. Sci. USA 1996, 93:13797-13801.
161. Wu S.M., Hallermeier K.M., Laue L., Brain C., Berry A.C., Grant D.B., Griffin J.E., Wilson J.D., Cutler G.B., Chan W.Y. Inactivation of the luteinizing hormone/chorionic gonadotropin receptor by an insertional mutation in Leydig cell hypoplasia. Mol. Endocrinol. 1998, 12:1651-1660.
162. Zarinan T., Perez-Solis M.A., Maya-Nunez G., Casas-Gonzalez P., Conn P.M., Dias J.A., Ulloa-Aguirre A. Dominant negative effects of human follicle-stimulating hormone receptor expression-deficient mutants on wild-type receptor cell surface expression. Rescue of oligomerization-dependent defective receptor expression by using cognate decoys. Mol. Cell. Endocrinol. 2010, 321:112-122.
163. Zhu X., Wess J. Truncated V2 vasopressin receptors as negative regulators of wild-type V2 receptor function. Biochemistry 1998, 37:15773-15784.