Rescue of expression and signaling of human luteinizing hormone G protein-coupled receptor mutants with an allosterically binding small-molecule agonist

Proceedings of the National Academy of Sciences of the United States of America

Volumn 108, Issue 17, 2011, Pages 7172-7176

  Newton, Claire L ^a   Whay, Adele M ^b   McArdle, Craig A ^c   Zhang, Meilin ^d   Van Koppen, Chris J ^e   Van De Lagemaat, Ruud ^e   Segaloff, Deborah L ^d   Millar, Robert P ^a,f,g  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b Vitrology   (United Kingdom)

^c UNIVERSITY OF BRISTOL   (United Kingdom)

^d UNIVERSITY OF IOWA   (United States)

^e MERCK RESEARCH LABORATORIES   (United States)

^f UNIVERSITY OF CAPE TOWN   (South Africa)

^g UNIVERSITY OF PRETORIA   (South Africa)

Author keywords

Infertility; Pharmacological chaperone; Receptor trafficking

Indexed keywords

CHAPERONE; G PROTEIN COUPLED RECEPTOR; LUTEINIZING HORMONE; MUTANT PROTEIN; ORG 42599; THIENOPYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ALLOSTERISM; ARTICLE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; DRUG RECEPTOR BINDING; HUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FOLDING; SIGNAL TRANSDUCTION;

ALLOSTERIC REGULATION; AMINO ACID SUBSTITUTION; CELL MEMBRANE; FEMALE; FERTILITY AGENTS; GENE EXPRESSION REGULATION; GLYCOSYLATION; HEK293 CELLS; HUMANS; INFERTILITY; LUTEINIZING HORMONE; MALE; MUTATION, MISSENSE; PROTEIN TRANSPORT; RECEPTORS, LH;

EID: 79955555416     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1015723108     Document Type: Article

References (29)

1. Kremer H, et al. (1995) Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet 9:160-164.
2. Misrahi M, et al. (1997) Comparison of immunocytochemical and molecular features with the phenotype in a case of incomplete male pseudohermaphroditism associated with a mutation of the luteinizing hormone receptor. J Clin Endocrinol Metab 82: 2159-2165. (Pubitemid 27287577)
3. Leung MY, et al. (2006) Biological effect of a novel mutation in the third leucine-rich repeat of human luteinizing hormone receptor. Mol Endocrinol 20:2493-2503. (Pubitemid 44496417)
4. Bruysters M, et al. (2008) A new LH receptor splice mutation responsible for male hypogonadism with subnormal sperm production in the propositus, and infertility with regular cycles in an affected sister. Hum Reprod 23:1917-1923. (Pubitemid 352020011)
5. Huhtaniemi I, Alevizaki M (2006) Gonadotrophin resistance. Best Pract Res Clin Endocrinol Metab 20:561-576. (Pubitemid 44872637)
6. Huhtaniemi IT, Themmen AP (2005) Mutations in human gonadotropin and gonadotropin-receptor genes. Endocrine 26:207-217. (Pubitemid 41271085)
7. Stavrou SS, et al. (1998) A novel mutation of the human luteinizing hormone receptor in 46XY and 46XX sisters. J Clin Endocrinol Metab 83:2091-2098. (Pubitemid 28496342)
8. Huhtaniemi IT, Themmen APN (2000) Mutations of gonadotropins and gonadotropin receptors: Elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 21:551-583.
9. Conn PM, Ulloa-Aguirre A, Ito J, Janovick JA (2007) G protein-coupled receptor trafficking in health and disease: Lessons learned to prepare for therapeutic mutant rescue in vivo. Pharmacol Rev 59:225-250. (Pubitemid 47481435)
10. Ellgaard L, Helenius A (2003) Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4:181-191. (Pubitemid 36288040)
11. Hebert DN, Molinari M (2007) In and out of the ER: Protein folding, quality control, degradation, and related human diseases. Physiol Rev 87:1377-1408. (Pubitemid 350041473)
12. Morello JP, Bichet DG (2001) Nephrogenic diabetes insipidus. Annu Rev Physiol 63: 607-630.
13. Noorwez SM, et al. (2003) Pharmacological chaperone-mediated in vivo folding and stabilization of the P23H-opsin mutant associated with autosomal dominant retinitis pigmentosa. J Biol Chem 278:14442-14450. (Pubitemid 36799997)
14. Janovick JA, Maya-Nunez G, Conn PM (2002) 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 87:3255-3262. (Pubitemid 34816374)
15. Millar RP, et al. (2004) Gonadotropin-releasing hormone receptors. Endocr Rev 25: 235-275. (Pubitemid 38501395)
16. Morello JP, et al. (2000) Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest 105:887-895.
17. Petäjä-Repo UE, et al. (2002) Ligands act as pharmacological chaperones and increase the efficiency of delta opioid receptor maturation. EMBO J 21:1628-1637. (Pubitemid 34614619)
18. van Straten NC, et al. (2002) The first orally active low molecular weight agonists for the LH receptor: Thienopyr(im)idines with therapeutic potential for ovulation induction. ChemBioChem 3:1023-1026.
19. van de Lagemaat R, et al. (2009) Induction of ovulation by a potent, orally active, low molecular weight agonist (Org 43553) of the luteinizing hormone receptor. Hum Reprod 24:640-648.
20. van Koppen CJ, et al. (2008) A signaling-selective, nanomolar potent allosteric low molecular weight agonist for the human luteinizing hormone receptor. Naunyn Schmiedebergs Arch Pharmacol 378:503-514.
21. Finch AR, Sedgley KR, Caunt CJ, McArdle CA (2008) Plasma membrane expression of GnRH receptors: Regulation by antagonists in breast, prostate, and gonadotrope cell lines. J Endocrinol 196:353-367. (Pubitemid 351298521)
22. Conn PM, Janovick JA (2009) Drug development and the cellular quality control system. Trends Pharmacol Sci 30:228-233.
23. Latronico AC, et al. (1996) Brief report: Testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone-receptor gene. N Engl J Med 334:507-512. (Pubitemid 26067739)
24. Mizrachi D, Segaloff DL (2004) Intracellularly located misfolded glycoprotein hormone receptors associate with different chaperone proteins than their cognate wild-type receptors. Mol Endocrinol 18:1768-1777. (Pubitemid 38859582)
25. Toledo SP, et al. (1996) An inactivating mutation of the luteinizing hormone receptor causes amenorrhea in a 46,XX female. J Clin Endocrinol Metab 81:3850-3854. (Pubitemid 26380385)
26. Black JW, Leff P (1983) Operational models of pharmacological agonism. Proc R Soc Lond B Biol Sci 220:141-162. (Pubitemid 14217337)
27. Bruysters M, Verhoef-Post M, Themmen AP (2008) Asp330 and Tyr331 in the Cterminal cysteine-rich region of the luteinizing hormone receptor are key residues in hormone-induced receptor activation. J Biol Chem 283:25821-25828.
28. Jaquette J, Segaloff DL (1997) Temperature sensitivity of some mutants of the lutropin/choriogonadotropin receptor. Endocrinology 138:85-91. (Pubitemid 27009409)
29. Qiao J, et al. (2009) A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism. Hum Mutat 30:E855-E865.