KISS1R Intracellular Trafficking and Degradation: Effect of the Arg386Pro Disease-Associated Mutation

Imagem de Miniatura
Arquivos
art_BIANCO_KISS1R_Intracellular_Trafficking_and_Degradation_Effect_of_the_2011.PDF (2.18 MB)
Citações na Scopus
56
Tipo de produção
article
Data de publicação
2011
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ENDOCRINE SOC
Autores
BIANCO, Suzy D. C.
VANDEPAS, Lauren
CORREA-MEDINA, Mayrin
GEREBEN, Balazs
MUKHERJEE, Abir
KUOHUNG, Wendy
CARROLL, Rona
KAISER, Ursula B.
Citação
ENDOCRINOLOGY, v.152, n.4, p.1616-1626, 2011
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The goal of this study was to investigate how the Arg386Pro mutation prolongs KiSS-1 receptor (KISS1R) responsiveness to kisspeptin, contributing to human central precocious puberty. Confocal imaging showed colocalization of wild-type (WT) KISS1R with a membrane marker, which persisted for up to 5 h of stimulation. Conversely, no colocalization with a lysosome marker was detected. Also, overnight treatment with a lysosome inhibitor did not affect WT KISS1R protein, whereas overnight treatment with a proteasome inhibitor increased protein levels by 24-fold. WT and Arg386Pro KISS1R showed time-dependent internalization upon stimulation. However, both receptors were recycled back to the membrane. The Arg386Pro mutation did not affect the relative distribution of KISS1R in membrane and internalized fractions when compared to WT KISS1R for up to 120 min of stimulation, demonstrating that this mutation does not affect KISS1R trafficking rate. Nonetheless, total Arg386Pro KISS1R was substantially increased compared with WT after 120 min of kisspeptin stimulation. This net increase was eliminated by blockade of detection of recycled receptors, demonstrating that recycled receptors account for the increased responsiveness of this mutant to kisspeptin. We therefore conclude the following: 1) WT KISS1R is degraded by proteasomes rather than lysosomes; 2) WT and Arg386Pro KISS1R are internalized upon stimulation, but most of the internalized receptors are recycled back to the membrane rather than degraded; 3) the Arg386Pro mutation does not affect the rate of KISS1R trafficking-instead, it prolongs responsiveness to kisspeptin by decreasing KISS1R degradation, resulting in the net increase on mutant receptor recycled back to the plasma membrane.(Endocrinology 152: 1616-1626,2011)
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/22662
Referências
  1. Teles MG, 2008, NEW ENGL J MED, V358, P709, DOI 10.1056/NEJMoa073443
  2. Ferguson SSG, 2001, PHARMACOL REV, V53, P1
  3. Silveira LG, 2010, J CLIN ENDOCR METAB, V95, P2276, DOI 10.1210/jc.2009-2421
  4. Luan XH, 2007, EUR J ENDOCRINOL, V157, P113, DOI 10.1530/EJE-07-0061
  5. Tarasova NI, 1997, J BIOL CHEM, V272, P14817, DOI 10.1074/jbc.272.23.14817
  6. Thompson EL, 2006, AM J PHYSIOL-ENDOC M, V291, pE1074, DOI 10.1152/ajpendo.00040.2006
  7. Blaukat A, 2001, J BIOL CHEM, V276, P40431, DOI 10.1074/jbc.M107024200
  8. Bianco SDC, 2009, NAT REV ENDOCRINOL, V5, P569, DOI 10.1038/nrendo.2009.177
  9. Luan X, 2007, NEUROENDOCRINOLOGY, V86, P77, DOI 10.1159/000107511
  10. Krupnick JG, 1997, J BIOL CHEM, V272, P18125, DOI 10.1074/jbc.272.29.18125
  11. Semple RK, 2005, J CLIN ENDOCR METAB, V90, P1849, DOI 10.1210/jc.2004-1418
  12. Matsui H, 2004, BIOCHEM BIOPH RES CO, V320, P383, DOI 10.1016/j.bbrc.2004.05.185
  13. Drake MT, 2006, CIRC RES, V99, P570, DOI 10.1161/01.RES.0000242563.47507.ce
  14. Seminara SB, 2006, ENDOCRINOLOGY, V147, P2122, DOI 10.1210/en.2005-1550
  15. Teles MG, 2010, EUR J ENDOCRINOL, V163, P29, DOI 10.1530/EJE-10-0012
  16. Palmert MR, 2003, MOL GENET METAB, V80, P1, DOI 10.1016/S1096-7192(03)00107-0
  17. Irwig MS, 2004, NEUROENDOCRINOLOGY, V80, P264, DOI 10.1159/000083140
  18. Chaturvedi K, 2001, J BIOL CHEM, V276, P12345, DOI 10.1074/jbc.M008054200
  19. Shenoy SK, 2001, SCIENCE, V294, P1307, DOI 10.1126/science.1063866
  20. de Roux N, 2003, P NATL ACAD SCI USA, V100, P10972, DOI 10.1073/pnas.1834399100
  21. Sagar GDV, 2007, MOL CELL BIOL, V27, P4774, DOI 10.1128/MCB.00283-07
  22. Navarro VM, 2004, ENDOCRINOLOGY, V145, P4565, DOI 10.1210/en.2004-0413
  23. Trarbach EB, 2007, PITUITARY, V10, P381, DOI 10.1007/s11102-007-0061-7
  24. Palmert MR, 2001, J CLIN ENDOCR METAB, V86, P2364, DOI 10.1210/jc.86.6.2364
  25. Gottsch ML, 2004, ENDOCRINOLOGY, V145, P4073, DOI 10.1210/en.2004-0431
  26. Hanyaloglu AC, 2008, ANNU REV PHARMACOL, V48, P537, DOI 10.1146/annurev.pharmtox.48.113006.094830
  27. Ritter SL, 2009, NAT REV MOL CELL BIO, V10, P819, DOI 10.1038/nrm2803
  28. Shahab M, 2005, P NATL ACAD SCI USA, V102, P2129, DOI 10.1073/pnas.0409822102
  29. Rocca A, 2001, MOL BIOL CELL, V12, P1293
  30. Lefkowitz RJ, 1998, J BIOL CHEM, V273, P18677, DOI 10.1074/jbc.273.30.18677
  31. Seminara SB, 2003, NEW ENGL J MED, V349, P1614, DOI 10.1056/NEJMoa035322
  32. Messager S, 2005, P NATL ACAD SCI USA, V102, P1761, DOI 10.1073/pnas.0409330102
  33. Roa J, 2008, AM J PHYSIOL-ENDOC M, V294, pE1088, DOI 10.1152/ajpendo.90240.2008
  34. Gurevich VV, 2006, PHARMACOL THERAPEUT, V110, P465, DOI 10.1016/j.pharmthera.2005.09.008
  35. Pampillo M, 2009, MOL ENDOCRINOL, V23, P2060, DOI 10.1210/me.2009-0013
  36. Balla T, 2009, TRENDS CELL BIOL, V19, P575, DOI 10.1016/j.tcb.2009.08.001
  37. Barak LS, 1997, MOL PHARMACOL, V51, P177
  38. Chan YM, 2009, PEPTIDES, V30, P42, DOI 10.1016/j.peptides.2008.06.015
  39. Galet C, 2006, MOL ENDOCRINOL, V20, P2931, DOI 10.1210/me.2006-0138
  40. GUREVICH VV, 1993, J BIOL CHEM, V268, P11628
  41. Hirasawa A, 1997, MOL PHARMACOL, V52, P764
  42. Iovane A, 2004, EUR J ENDOCRINOL, V151, pU83, DOI 10.1530/eje.0.151U083
  43. KUOHUNG W, J BIOMOL SC IN PRESS, V15, P508
  44. Moore RH, 1999, J CELL SCI, V112, P329
  45. Mosser Valerie A, 2008, J Mol Signal, V3, P20, DOI 10.1186/1750-2187-3-20
  46. PALCZEWSKI K, 1991, J BIOL CHEM, V266, P12949
  47. Perret BG, 2003, PROTEIN EXPRES PURIF, V31, P123, DOI 10.1016/S1046-5928(03)00140-2
  48. Tenenbaum-Rakover Y, 2007, J CLIN ENDOCR METAB, V92, P1137, DOI 10.1210/jc.2006-2147
  49. Vogel G, 2005, SCIENCE, V309, P551, DOI 10.1126/science.309.5734.551
  50. Xu ZQD, 2007, ACTA PHYSIOL, V190, P39, DOI 10.1111/j.1748-1716.2007.01695.x

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/42