Gastroenterology
Volume 123, Issue 4 , Pages 1135-1143 , October 2002

Neurotensin receptor–1 and –3 complex modulates the cellular signaling of neurotensin in the HT29 cell line

Received 25 March 2002 ,Accepted 27 June 2002.

References 

  1. Bouvier M. Oligomerization of G-protein-coupled transmitter receptors. Nat Rev Neurosci. 2001;2:274–286
  2. Devi LA. Heterodimerization of G-protein-coupled receptors: pharmacology, signaling and trafficking. Trends Pharmacol Sci. 2001;22:532–537
  3. Hebert TE, Moffett S, Morello JP, Loisel TP, Bichet DG, Barret C, et al. A peptide derived from a beta2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J Biol Chem. 1996;271:16384–16392
  4. Angers S, Salahpour A, Joly E, Hilairet S, Chelsky D, Dennis M, et al. Detection of beta2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET). Proc Natl Acad Sci U S A. 2000;97:3684–3689
  5. Cvejic S, Devi LA. Dimerization of the delta opioid receptor: implication for a role in receptor internalization. J Biol Chem. 1997;272:26959–26964
  6. Rocheville M, Lange DC, Kumar U, Sasi R, Patel RC, Patel YC. Subtypes of the somatostatin receptor assemble as functional homo- and heterodimers. J Biol Chem. 2000;275:7862–7869
  7. Jordan BA, Trapaidze N, Gomes I, Nivarthi R, Devi LA. Oligomerization of opioid receptors with beta 2-adrenergic receptors: a role in trafficking and mitogen-activated protein kinase activation. Proc Natl Acad Sci U S A. 2001;98:343–348
  8. Rocheville M, Lange DC, Kumar U, Patel SC, Patel RC, Patel YC. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science. 2000;288:154–157
  9. Jones KA, Borowsky B, Tamm JA, Craig DA, Durkin MM, Dai M, et al. GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2. Nature. 1998;396:674–679
  10. Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, et al. GABA(B)-receptor subtypes assemble into functional heteromeric complexes. Nature. 1998;396:683–687
  11. White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, et al. Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature. 1998;396:679–682
  12. Maudsley S, Pierce KL, Zamah AM, Miller WE, Ahn S, Daaka Y, et al. The beta(2)-adrenergic receptor mediates extracellular signal-regulated kinase activation via assembly of a multi-receptor complex with the epidermal growth factor receptor. J Biol Chem. 2000;275:9572–9580
  13. Vincent JP, Mazella J, Kitabgi P. Neurotensin and neurotensin receptors. Trends Pharmacol Sci. 1999;20:302–309
  14. Tanaka K, Masu M, Nakanishi S. Structure and functional expression of the cloned rat neurotensin receptor. Neuron. 1990;4:847–854
  15. Chabry J, Labbe-Jullie C, Gully D, Kitabgi P, Vincent JP, Mazella J. Stable expression of the cloned rat brain neurotensin receptor into fibroblasts: binding properties, photoaffinity labeling, transduction mechanisms, and internalization. J Neurochem. 1994;63:19–27
  16. Hermans E, Maloteaux JM, Octave JN. Phospholipase C activation by neurotensin and neuromedin N in Chinese hamster ovary cells expressing the rat neurotensin receptor. Brain Res Mol Brain Res. 1992;15:332–338
  17. Poinot-Chazel C, Portier M, Bouaboula M, Vita N, Pecceu F, Gully D, et al. Activation of mitogen-activated protein kinase couples neurotensin receptor stimulation to induction of the primary response gene Krox-24. Biochem J. 1996;320:145–151
  18. Nemeroff CB. The interaction of neurotensin with dopaminergic pathways in the central nervous system: basic neurobiology and implications for the pathogenesis and treatment of schizophrenia. Psychoneuroendocrinology. 1986;11:15–37
  19. Dubuc I, Sarret P, Labbe-Jullie C, Botto JM, Honore E, Bourdel E, et al. Identification of the receptor subtype involved in the analgesic effect of neurotensin. J Neurosci. 1999;19:503–510
  20. Petersen CM, Nielsen MS, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen HH, et al. Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography. J Biol Chem. 1997;272:3599–3605
  21. Mazella J, Zsurger N, Navarro V, Chabry J, Kaghad M, Caput D, et al. The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor. J Biol Chem. 1998;273:26273–26276
  22. Marcusson EG, Horazdovsky BF, Cereghino JL, Gharakhanian E, Emr SD. The sorting receptor for yeast vacuolar carboxypeptidase Y is encoded by the VPS10 gene. Cell. 1994;77:579–586
  23. Munck Petersen C, Nielsen MS, Jacobsen C, Tauris J, Jacobsen L, Gliemann J, et al. Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding. EMBO J. 1999;18:595–604
  24. Nielsen MS, Jacobsen C, Olivecrona G, Gliemann J, Petersen CM. Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase. J Biol Chem. 1999;274:8832–8836
  25. Yamada M, Ohata H, Momose K, Richelson E. Pharmacological characterization of SR 48692 sensitive neurotensin receptor in human pancreatic cancer cells, MIA PaCa-2. Res Commun Mol Pathol Pharmacol. 1995;90:37–47
  26. Sehgal I, Powers S, Huntley B, Powis G, Pittelkow M, Maihle NJ. Neurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer. Proc Natl Acad Sci U S A. 1994;91:4673–4677
  27. Seethalakshmi L, Mitra SP, Dobner PR, Menon M, Carraway RE. Neurotensin receptor expression in prostate cancer cell line and growth effect of NT at physiological concentrations. Prostate. 1997;31:183–192
  28. Iwase K, Evers BM, Hellmich MR, Kim HJ, Higashide S, Gully D, et al. Indirect inhibitory effect of a neurotensin receptor antagonist on human colon cancer (LoVo) growth. Surg Oncol. 1996;5:245–251
  29. Maoret JJ, Anini Y, Rouyer-Fessard C, Gully D, Laburthe M. Neurotensin and a non-peptide neurotensin receptor antagonist control human colon cancer cell growth in cell culture and in cells xenografted into nude mice. Int J Cancer. 1999;80:448–454
  30. Dal Farra C, Sarret P, Navarro V, Botto JM, Mazella J, Vincent JP. Involvement of the neurotensin receptor subtype NTR3 in the growth effect of neurotensin on cancer cell lines. Int J Cancer. 2001;92:503–509
  31. Sadoul JL, Mazella J, Amar S, Kitabgi P, Vincent JP. Preparation of neurotensin selectively iodinated on the tyrosine 3 residue. Biological activity and binding properties on mammalian neurotensin receptors. Biochem Biophys Res Commun. 1984;120:812–819
  32. Mazella J, Kitabgi P, Vincent JP. Molecular properties of neurotensin receptors in rat brain. Identification of subunits by covalent labeling. J Biol Chem. 1985;260:508–514
  33. Cullen BR. Use of eukaryotic expression technology in the functional analysis of cloned genes. Methods Enzymol. 1987;152:684–704
  34. Navarro V, Martin S, Sarret P, Nielsen MS, Petersen CM, Vincent JP, et al. Pharmacological properties of the mouse neurotensin receptor 3. Maintenance of cell surface receptor during internalization of neurotensin. FEBS Lett. 2001;495:100–105
  35. Vandenbulcke F, Nouel D, Vincent JP, Mazella J, Beaudet A. Ligand-induced internalization of neurotensin in COS-7 transfected cells: differential intracellular trafficking of ligand and receptor. J Cell Sci. 2000;113:2963–2975
  36. Chabry J, Gaudriault G, Vincent JP, Mazella J. Implication of various forms of neurotensin receptors in the mechanism of internalization of neurotensin in cerebral neurons. J Biol Chem. 1993;268:17138–17144
  37. Zhang J, Barak LS, Anborgh PH, Laporte SA, Caron MG, Fergusson SSG. Cellular trafficking of G protein-coupled receptor/β-arrestin endocytic complexes. J Biol Chem. 1999;274:10999–11006
  38. Abdalla S, Lother H, el Massiery A, Quitterer U. Increased AT1 receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med. 2001;7:1003–1009
  39. McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature. 1998;393:333–339
  40. Christopoulos G, Perry KJ, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, et al. Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Mol Pharmacol. 1999;56:235–242
  41. Muff R, Buhlmann N, Fischer JA, Born W. An amylin receptor is revealed following co-transfection of a calcitonin receptor with receptor activity modifying proteins-1 or -3. Endocrinology. 1999;140:2924–2927

 Address requests for reprints to: Jean Mazella, Ph.D., Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097 du Centre National de la Recherche Scientifique, 660 route des lucioles, Sophia Antipolis, 06560 Valbonne, France. e-mail: mazella@ipmc.cnrs.fr; fax: (33) 4-93957708.

☆☆ S.M. and V.N. are fellowship recipients of the Association pour la Recherche contre le Cancer (ARC).

 The authors thank P. Kitabgi for complementary DNA encoding the human NTR1, M. S. Nielsen and C. M. Petersen (University of Aarhus, Denmark) for the gift of anti-sortilin/NTR3 and anti-propeptide antibodies and of sortilin-expressing CHO cells.

PII: S0016-5085(02)00219-6

doi: 10.1053/gast.2002.36000

Gastroenterology
Volume 123, Issue 4 , Pages 1135-1143 , October 2002