(Journal Article): Pharmacochaperones post-translationally enhance cell surface expression by increasing conformational stability of wild-type and mutant vasopressin V2 receptors
 
Wuller S, Wiesner B, Loffler A, Furkert J, Krause G, Hermosilla R, Schaefer M, Schulein R, Rosenthal W, Oksche A (Charite, Institut fur Pharmakologie, Berlin 14195, Germany, alexander.oksche@medizin.fu-berlin.de )
 
IN: J Biol Chem 2004; 279(45):47254-47263
Impact Factor(s) of J Biol Chem: 6.355 (2004), 6.482 (2003), 7.258 (2001)

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ABSTRACT: Some membrane-permeable antagonists restore cell surface expression of misfolded receptors retained in the endoplasmic reticulum (ER) and are therefore termed pharmacochaperones. Whether pharmacochaperones increase protein stability, thereby preventing rapid degradation, or assist folding via direct receptor interactions or interfere with quality control components remains elusive. We now show that the cell surface expression and function (binding of the agonist) of the mainly ER-retained wild-type murine vasopressin V2 receptor.GFP fusion protein (mV2R.GFP) is restored by the vasopressin receptor antagonists SR49059 and SR121463B with EC50 values similar to their KD values. This effect was preserved when protein synthesis was abolished. In addition, SR121463B rescued eight mutant human V2Rs (hV2Rs; three are responsible for nephrogenic diabetes insipidus) characterized by amino acid exchanges at the C-terminal end of transmembrane helix TMI and TMVII. In contrast, mutants with amino acid exchanges at the interface of TM II and IV were not rescued by either antagonist. The mechanisms involved in successful rescue of cell surface delivery are explained in a 3D homology model of the antagonist-bound hV2R.

REFERENCES:

  1. Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, Antaramian A, Brabet P, Rosenthal W. Molecular cloning of the receptor for human antidiuretic hormone. Nature 1992. 357(6376):333-335.
  2. Rosenthal W, Seibold A, Antaramian A, Lonergan M, Arthus MF, Hendy GN, Birnbaumer M, Bichet DG. Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus. Nature 1992. 359(6392):233-235.
  3. Oksche A, Rosenthal W. The molecular basis of nephrogenic diabetes insipidus. J Mol Med 1998. 76(5):326-337.
  4. Morello JP, Salahpour A, Petäjä-Repo UE, Laperriere A, Lonergan M, Arthus MF, Nabi IR, Bichet DG, Bouvier M. Association of calnexin with wild type and mutant AVPR2 that causes nephrogenic diabetes insipidus. Biochemistry 2001. 40(23):6766-6775.
  5. 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(Pt 14):2907-2918.
  6. Noorwez SM, Kuksa V, Imanishi Y, Zhu L, Filipek S, Palczewski K, Kaushal S. Pharmacological chaperone-mediated in vivo folding and stabilization of the P23H-opsin mutant associated with autosomal dominant retinitis pigmentosa. J Biol Chem 2003. 278(16):14442-14450.
  7. Morello JP, Salahpour A, Laperriere A, Bernier V, Arthus MF, Lonergan M, Petäjä-Repo U, Angers S, Morin D, Bichet DG, Bouvier M. Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest 2000. 105(7):887-895.
  8. 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(7):3255-3262.
  9. Oksche A, Leder G, Valet S, Platzer M, Hasse K, Geist S, Krause G, Rosenthal A, Rosenthal W. 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(4):799-813.
  10. Oksche A, Dehe M, Schülein R, Wiesner B, Rosenthal W. Folding and cell surface expression of the vasopressin V2 receptor: requirement of the intracellular C-terminus. FEBS Lett 1998. 424(1-2):57-62.
  11. Gregan B, Jürgensen J, Papsdorf G, Furkert J, Schaefer M, Beyermann M, Rosenthal W, Oksche A. Ligand-dependent differences in the internalization of endothelin A and endothelin B receptor heterodimers. J Biol Chem 2004. 279(26):27679-27687.
  12. Hermosilla R, Schülein R. Sorting functions of the individual cytoplasmic domains of the G protein-coupled vasopressin V(2) receptor in Madin Darby canine kidney epithelial cells. Mol Pharmacol 2001. 60(5):1031-1039.
  13. Maric K, Oksche A, Rosenthal W. Aquaporin-2 expression in primary cultured rat inner medullary collecting duct cells. Am J Physiol 1998. 275(5 Pt 2):F796-F801.
  14. Amiri H, Schultz G, Schaefer M. FRET-based analysis of TRPC subunit stoichiometry. Cell Calcium 2003. 33(5-6):463-470.
  15. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M. Crystal structure of rhodopsin: A G protein-coupled receptor. Science 2000. 289(5480):739-745.
  16. Krause G, Hermosilla R, Oksche A, Rutz C, Rosenthal W, Schülein R. Molecular and conformational features of a transport-relevant domain in the C-terminal tail of the vasopressin V(2) receptor. Mol Pharmacol 2000. 57(2):232-242.
  17. Tahtaoui C, Balestre MN, Klotz P, Rognan D, Barberis C, Mouillac B, Hibert M. Identification of the binding sites of the SR49059 nonpeptide antagonist into the V1a vasopressin receptor using sulfydryl-reactive ligands and cysteine mutants as chemical sensors. J Biol Chem 2003. 278(41):40010-40019.
  18. Case DA, Pearlman DA, Caldwell JW, Cheatham TE III, Ross WS, Simmerling CL, Darden TA, Merz KM, Stanton RV, Cheng AL, Vincent JJ, Crowley M, Tsui V, Radmer RJ, Duan Y, Pitera J, Massova I, Seibel GL, Singh UC, Weiner PK, Kollman PA. AMBER 5.0., 1998, University of California, San Francisco.
  19. Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S, Fish A, Whitley CB, Jaeger P, Gertner J, New M, DiBona FJ, Kaplan BS, Robertson GL, Hendy GN, Fujiwara TM, Morgan K. Am J Hum Genet 1994. 55:278-286.
  20. Yuasa H, Ito M, Oiso Y, Kurokawa M, Watanabe T, Oda Y, Ishizuka T, Tani N, Ito S, Shibata A, Saito H. Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus. J Clin Endocrinol Metab 1994. 79(2):361-365.
  21. Oksche A, Schülein R, Rutz C, Liebenhoff U, Dickson J, Müller H, Birnbaumer M, Rosenthal W. Vasopressin V2 receptor mutants that cause X-linked nephrogenic diabetes insipidus: analysis of expression, processing, and function. Mol Pharmacol 1996. 50(4):820-828.
  22. Ala Y, Morin D, Mouillac B, Sabatier N, Vargas R, Cotte N, Dechaux M, Antignac C, Arthus MF, Lonergan M, Turner MS, Balestre MN, Alonso G, Hibert M, Barberis C, Hendy GN, Bichet DG, Jard S. Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype. J Am Soc Nephrol 1998. 9(10):1861-1872.
  23. Arthus MF, Lonergan M, Crumley MJ, Naumova AK, Morin D, De Marco LA, Kaplan BS, Robertson GL, Sasaki S, Morgan K, Bichet DG, Fujiwara TM. Report of 33 novel AVPR2 mutations and analysis of 117 families with X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 2000. 11(6):1044-1054.
  24. Terrillon S, Durroux T, Mouillac B, Breit A, Ayoub MA, Taulan M, Jockers R, Barberis C, Bouvier M. Oxytocin and vasopressin V1a and V2 receptors form constitutive homo- and heterodimers during biosynthesis. Mol Endocrinol 2003. 17(4):677-691.
  25. Cosson P, Lefkir Y, Demolliere C, Letourneur F. New COP1-binding motifs involved in ER retrieval. EMBO J 1998. 17(23):6863-6870.
  26. Baldwin JM, Schertler GF, Unger VM. An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors. J Mol Biol 1997. 272(1):144-164.
  27. Schülein R, Zühlke K, Oksche A, Hermosilla R, Furkert J, Rosenthal W. The role of conserved extracellular cysteine residues in vasopressin V2 receptor function and properties of two naturally occurring mutant receptors with additional extracellular cysteine residues. FEBS Lett 2000. 466(1):101-106.
  28. Tan CM, Nickols HH, Limbird LE. Appropriate polarization following pharmacological rescue of V2 vasopressin receptors encoded by X-linked nephrogenic diabetes insipidus alleles involves a conformation of the receptor that also attains mature glycosylation. J Biol Chem 2003. 278(37):35678-35686.
  29. Foster BA, Coffey HA, Morin MJ, Rastinejad F. Pharmacological rescue of mutant p53 conformation and function. Science 1999. 286(5449):2507-2510.
  30. Issaeva N, Friedler A, Bozko P, Wiman KG, Fersht AR, Selivanova G. Rescue of mutants of the tumor suppressor p53 in cancer cells by a designed peptide. Proc Natl Acad Sci U S A 2003. 100(23):13303-13307.


 
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