Normal testicular function without detectable follicle-stimulating hormone. A novel mutation in the follicle-stimulating hormone receptor gene leading to apparent constitutive activity and impaired agonist-induced desensitization and internalization

Molecular and Cellular Endocrinology

Volumn 364, Issue 1-2, 2012, Pages 71-82

  Casas González, Patricia ^a   Scaglia, Hugo E ^b   Pérez Solís, Marco A ^a   Durand, Guillaume ^c,d,e,f   Scaglia, Javier ^b   Zariñán, Teresa ^a   Dias, James A ^g   Reiter, Eric ^c,d,e,f   Ulloa Aguirre, Alfredo ^h  

^a Hospital Luis Castelazo Ayala   (Mexico)

^b HOSPITAL ITALIANO DE BUENOS AIRES   (Argentina)

^c UMR85 PHYSIOLOGIE DE LA REPRODUCTION ET DES COMPORTEMENTS   (France)

^d CNRS   (France)

^e UNIVERSITÉ DE TOURS   (France)

^f IFCE   (France)

^g STATE UNIVERSITY OF NEW YORK   (United States)

^h INSTITUTO NACIONAL DE SALUD PÚBLICA   (Mexico)

Author keywords

Constitutive activation; Desensitization; Follicle stimulating hormone; Follicle stimulating hormone receptor; Internalization; Mutation

Indexed keywords

CYCLIC AMP; FOLLITROPIN RECEPTOR; FORSKOLIN; MUTANT PROTEIN; RECEPTOR PROTEIN;

ADULT; AMINO ACID SEQUENCE; ARTICLE; CASE REPORT; CELL STRAIN HEK293; CELL SURFACE; CONTROLLED STUDY; DESENSITIZATION; FSHR GENE; GENE; GENE MUTATION; HORMONE ACTION; HUMAN; HUMAN CELL; INTERNALIZATION; MALE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TESTIS FUNCTION;

ARRESTINS; BASE SEQUENCE; CYCLIC AMP; FOLLICLE STIMULATING HORMONE; GENES, REPORTER; HEK293 CELLS; HUMANS; LUCIFERASES; MALE; MOLECULAR SEQUENCE DATA; MUTATION; PHENOTYPE; RECEPTORS, FSH; SPERMATOGENESIS; TESTIS; TRANSFECTION; YOUNG ADULT;

EID: 84867547959     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2012.08.011     Document Type: Article

References (58)

1. Akada R., Hirosawa I., Hoshida H., Nishizawa Y. Detection of a point mutation in FAS2 gene of sake yeast strains by allele-specific PCR amplification. J. Biosci. Bioeng. 2001, 92:189-192.
2. Alewijnse A.E., Smit M.J., Rodriguez Pena M.S., Verzijl D., Timmerman H., Leurs R. Modulation of forskolin-mediated adenylyl cyclase activation by constitutively active G(S)-coupled receptors. FEBS Lett. 1997, 419:171-174.
3. 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.
4. Ascoli M. Functional consequences of the phosphorylation of the gonadotropin receptors. Biochem. Pharmacol. 1996, 52:1647-1655.
5. Costagliola S., Urizar E., Mendive F., Vassart G. Specificity and promiscuity of gonadotropin receptors. Reproduction 2005, 130:275-281.
6. De Leener A., Montanelli L., Van Durme J., Chae H., Smits G., Vassart G., Costagliola S. Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology. J. Clin. Endocrinol. Metab. 2006, 91:555-562.
7. 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.
8. DiPilato L.M., Cheng X., Zhang J. Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments. Proc. Natl. Acad. Sci. USA 2004, 101:16513-16518.
9. Dupakuntla M., Mahale S.D. Accessibility of the extracellular loops of follicle stimulating hormone receptor and their role in hormone-receptor interaction. Mol. Cell. Endocrinol. 2010, 315:131-137.
10. Freedman N.J., Lefkowitz R.J. Desensitization of G protein-coupled receptors. Recent Prog. Horm. Res. 1996, 51:319-351.
11. Frenzel R., Voigt C., Paschke R. The human thyrotropin receptor is predominantly internalized by beta-arrestin 2. Endocrinology 2006, 147:3114-3122.
12. Fuhrer D., Holzapfel H.P., Wonerow P., Scherbaum W.A., Paschke R. Somatic mutations in the thyrotropin receptor gene and not in the Gs alpha protein gene in 31 toxic thyroid nodules. J. Clin. Endocrinol. Metab. 1997, 82:3885-3891.
13. 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.
14. Huhtaniemi I.T., Themmen A.P. Mutations in human gonadotropin and gonadotropin-receptor genes. Endocrine 2005, 26:207-217.
15. Ji I., Ji T.H. Differential roles of exoloop 1 of the human follicle-stimulating hormone receptor in hormone binding and receptor activation. J. Biol. Chem. 1995, 270:15970-15973.
16. Kara E., Crepieux P., Gauthier C., Martinat N., Piketty V., Guillou F., Reiter E. A phosphorylation cluster of five serine and threonine residues in the C-terminus of the follicle-stimulating hormone receptor is important for desensitization but not for beta-arrestin-mediated ERK activation. Mol. Endocrinol. 2006, 20:3014-3026.
17. Kluetzman K.S., Thomas R.M., Nechamen C.A., Dias J.A. Decreased degradation of internalized follicle-stimulating hormone caused by mutation of aspartic acid 6.30(550) in a protein kinase-CK2 consensus sequence in the third intracellular loop of human follicle-stimulating hormone receptor. Biol. Reprod. 2011, 84:1154-1163.
18. Koenig J.A., Edwardson J.M. Endocytosis and recycling of G protein-coupled receptors. Trends Pharmacol. Sci. 1997, 18:276-287.
19. Krishnamurthy H., Galet C., Ascoli M. The association of arrestin-3 with the follitropin receptor depends on receptor activation and phosphorylation. Mol. Cell. Endocrinol. 2003, 204:127-140.
20. Krishnamurthy H., Kishi H., Shi M., Galet C., Bhaskaran R.S., Hirakawa T., Ascoli M. Postendocytotic trafficking of the follicle-stimulating hormone (FSH)-FSH receptor complex. Mol. Endocrinol. 2003, 17:2162-2176.
21. Krupnick J.G., Santini F., Gagnon A.W., Keen J.H., Benovic J.L. Modulation of the arrestin-clathrin interaction in cells. Characterization of beta-arrestin dominant-negative mutants. J. Biol. Chem. 1997, 272:32507-32512.
22. Lazari M.F., Liu X., Nakamura K., Benovic J.L., Ascoli M. Role of G protein-coupled receptor kinases on the agonist-induced phosphorylation and internalization of the follitropin receptor. Mol. Endocrinol. 1999, 13:866-878.
23. Lindau-Shepard B., Roth K.E., Dias J.A. Identification of amino acids in the C-terminal region of human follicle-stimulating hormone (FSH) beta-subunit involved in binding to human FSH receptor. Endocrinology 1994, 135:1235-1240.
24. Meduri G., Bachelot A., Cocca M.P., Vasseur C., Rodien P., Kuttenn F., Touraine P., Misrahi M. Molecular pathology of the FSH receptor: new insights into FSH physiology. Mol. Cell. Endocrinol. 2008, 282:130-142.
25. Montanelli L., Delbaere A., Di Carlo C., Nappi C., Smits G., Vassart G., Costagliola S. A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome. J. Clin. Endocrinol. Metab. 2004, 89:1255-1258.
26. 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.
27. Nakamura K., Hipkin R.W., Ascoli M. The agonist-induced phosphorylation of the rat follitropin receptor maps to the first and third intracellular loops. Mol. Endocrinol. 1998, 12:580-591.
28. Nakamura K., Krupnick J.G., Benovic J.L., Ascoli M. Signaling and phosphorylation-impaired mutants of the rat follitropin receptor reveal an activation- and phosphorylation-independent but arrestin-dependent pathway for internalization. J. Biol. Chem. 1998, 273:24346-24354.
29. Nechamen C.A., Dias J.A. Point mutations in follitropin receptor result in ER retention. Mol. Cell. Endocrinol. 2003, 201:123-131.
30. Nguyen K., Kassimatis T., Lymperopoulos A. Impaired desensitization of a human polymorphic alpha2B-adrenergic receptor variant enhances its sympatho-inhibitory activity in chromaffin cells. Cell. Commun. Signal. 2011, 9:5.
31. Parma J., Duprez L., Van Sande J., Cochaux P., Gervy C., Mockel J., Dumont J., Vassart G. Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 1993, 365:649-651.
32. 2+ cascades. Mol. Endocrinol. 1995, 9:725-733.
33. Parnot C., Miserey-Lenkei S., Bardin S., Corvol P., Clauser E. Lessons from constitutively active mutants of G protein-coupled receptors. Trends Endocrinol. Metab. 2002, 13:336-343.
34. Pei G., Samama P., Lohse M., Wang M., Codina J., Lefkowitz R.J. A constitutively active mutant beta 2-adrenergic receptor is constitutively desensitized and phosphorylated. Proc. Natl. Acad. Sci. USA 1994, 91:2699-2702.
35. Pitcher J.A., Freedman N.J., Lefkowitz R.J. G protein-coupled receptor kinases. Annu. Rev. Biochem. 1998, 67:653-692.
36. Quellari M., Desroches A., Beau I., Beaudeux E., Misrahi M. Role of cleavage and shedding in human thyrotropin receptor function and trafficking. Eur. J. Biochem. 2003, 270:3486-3497.
37. Reiter E., Ahn S., Shukla A.K., Lefkowitz R.J. Molecular mechanism of beta-arrestin-biased agonism at seven-transmembrane receptors. Annu. Rev. Pharmacol. Toxicol. 2012, 52:179-197.
38. Reiter E., Lefkowitz R.J. GRKs and beta-arrestins: roles in receptor silencing, trafficking and signaling. Trends Endocrinol. Metab. 2006, 17:159-165.
39. Scaglia H.E., Carrere C.A., Mariani V.A., Zylbersztein C.C., Rey-Valzacchi G.J., Kelly E.E., Aquilano D.R. Altered testicular hormone production in infertile patients with idiopathic oligoasthenospermia. J. Androl. 1991, 12:273-280.
40. Simoni M., Gromoll J., Nieschlag E. The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr. Rev. 1997, 18:739-773.
41. Smits G., Olatunbosun O., Delbaere A., Pierson R., Vassart G., Costagliola S. Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor. N. Engl. J. Med. 2003, 349:760-766.
42. Swords F.M., Baig A., Malchoff D.M., Malchoff C.D., Thorner M.O., King P.J., Hunyady L., Clark A.J. Impaired desensitization of a mutant adrenocorticotropin receptor associated with apparent constitutive activity. Mol. Endocrinol. 2002, 16:2746-2753.
43. Tao Y.X. Constitutive activation of G protein-coupled receptors and diseases: insights into mechanisms of activation and therapeutics. Pharmacol. Ther. 2008, 120:129-148.
44. 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.
45. Tonacchera M., Agretti P., Rosellini V., Ceccarini G., Perri A., Zampolli M., Longhi R., Larizza D., Pinchera A., Vitti P., Chiovato L. Sporadic nonautoimmune congenital hyperthyroidism due to a strong activating mutation of the thyrotropin receptor gene. Thyroid 2000, 10:859-863.
46. 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 A189V mutation. Mol. Cell. Endocrinol. 2011, 331:109-118.
47. Troispoux C., Guillou F., Elalouf J.M., Firsov D., Iacovelli L., De Blasi A., Combarnous Y., Reiter E. Involvement of G protein-coupled receptor kinases and arrestins in desensitization to follicle-stimulating hormone action. Mol. Endocrinol. 1999, 13:1599-1614.
48. 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.
49. 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.).
50. 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.
51. Ulloa-Aguirre A., Timossi C. Structure-function relationship of follicle-stimulating hormone and its receptor. Hum. Reprod. Update 1998, 4:260-283.
52. Ulloa-Aguirre A., Zarinan T., Pasapera A.M., Casas-Gonzalez P., Dias J.A. Multiple facets of follicle-stimulating hormone receptor function. Endocrine 2007, 32:251-263.
53. 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.
54. Vassart G., Pardo L., Costagliola S. A molecular dissection of the glycoprotein hormone receptors. Trends Biochem. Sci. 2004, 29:119-126.
55. Vasseur C., Rodien P., Beau I., Desroches A., Gerard C., de Poncheville L., Chaplot S., Savagner F., Croue A., Mathieu E., Lahlou N., Descamps P., Misrahi M. A chorionic gonadotropin-sensitive mutation in the follicle-stimulating hormone receptor as a cause of familial gestational spontaneous ovarian hyperstimulation syndrome. N. Engl. J. Med. 2003, 349:753-759.
56. Vlaeminck-Guillem V., Ho S.C., Rodien P., Vassart G., Costagliola S. Activation of the cAMP pathway by the TSH receptor involves switching of the ectodomain from a tethered inverse agonist to an agonist. Mol. Endocrinol. 2002, 16:736-746.
57. Zambrano E., Barrios-de-Tomasi J., Cardenas M., Ulloa-Aguirre A. Studies on the relative in-vitro biological potency of the naturally-occurring isoforms of intrapituitary follicle stimulating hormone. Mol. Hum. Reprod. 1996, 2:563-571.
58. Zhang J., Ma Y., Taylor S.S., Tsien R.Y. Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering. Proc. Natl. Acad. Sci. USA 2001, 98:14997-15002.