%0 Journal Article %1 hwang_intermolecular_2010 %A Hwang, Jae Ryoung %A Baek, Min Woo %A Sim, Jeonggu %A Choi, Heung-Sik %A Han, Ji Man %A Kim, You Lim %A Hwang, Jong-Ik %A Kwon, Hyuk Bang %A Beaudet, Nicolas %A Sarret, Philippe %A Seong, Jae Young %D 2010 %J Biochemical and Biophysical Research Communications %K Animals Cell_Line Hela_Cells Humans Neurotensin Protein_Interaction_Mapping Protein_Multimerization Protein_Structure Rats Receptors Tertiary %N 1 %P 1007--1013 %R 10.1016/j.bbrc.2009.12.007 %T Intermolecular cross-talk between NTR1 and NTR2 neurotensin receptor promotes intracellular sequestration and functional inhibition of NTR1 receptors %U http://www.ncbi.nlm.nih.gov/pubmed/19968961 %V 391 %X G-protein-coupled receptors (GPCR) are now regarded as being able to acquire heterodimer conformations affecting their pharmacology, signaling and trafficking. In co-immunoprecipitation studies using differentially epitope-tagged receptors, we herein provide direct evidence for heterodimerization of human neurotensin type 1 receptor (hNTR1) and type 2 receptor (hNTR2). Using chimeric constructs, we also identified the hNTR2 transmembrane 2 (TM2) to TM4 region as crucial for the formation of the dimerization interface. At the functional level, we demonstrated that the co-expression of hNTR2 suppressed hNTR1-mediated adenylate cyclase/cAMP and phospholipase C activation. Finally, confocal microscopy revealed that whereas tagged hNTR1 expressed alone were localized to the plasma membrane, co-expression of hNTR2 caused the retention of hNTR1 in sub-cellular compartments, indicating that heterodimerization with hNTR2 interferes with the proper recruitment of hNTR1 to the plasma membrane. Overall, this study proposes a novel function of NTR2 in the regulation of NTR1 activity.

@article{hwang_intermolecular_2010, abstract = {G-protein-coupled receptors {(GPCR)} are now regarded as being able to acquire heterodimer conformations affecting their pharmacology, signaling and trafficking. In co-immunoprecipitation studies using differentially epitope-tagged receptors, we herein provide direct evidence for heterodimerization of human neurotensin type 1 receptor {(hNTR1)} and type 2 receptor {(hNTR2).} Using chimeric constructs, we also identified the {hNTR2} transmembrane 2 {(TM2)} to {TM4} region as crucial for the formation of the dimerization interface. At the functional level, we demonstrated that the co-expression of {hNTR2} suppressed {hNTR1-mediated} adenylate {cyclase/cAMP} and phospholipase C activation. Finally, confocal microscopy revealed that whereas tagged {hNTR1} expressed alone were localized to the plasma membrane, co-expression of {hNTR2} caused the retention of {hNTR1} in sub-cellular compartments, indicating that heterodimerization with {hNTR2} interferes with the proper recruitment of {hNTR1} to the plasma membrane. Overall, this study proposes a novel function of {NTR2} in the regulation of {NTR1} activity.}, added-at = {2011-08-03T17:38:07.000+0200}, author = {Hwang, Jae Ryoung and Baek, Min Woo and Sim, Jeonggu and Choi, {Heung-Sik} and Han, Ji Man and Kim, You Lim and Hwang, {Jong-Ik} and Kwon, Hyuk Bang and Beaudet, Nicolas and Sarret, Philippe and Seong, Jae Young}, biburl = {https://www.bibsonomy.org/bibtex/24559b64cfbaf7a6800778df263d1bfac/crc_chus}, doi = {10.1016/j.bbrc.2009.12.007}, interhash = {1b88d42d5f5ffd4e1e6681bafd17687f}, intrahash = {4559b64cfbaf7a6800778df263d1bfac}, issn = {1090-2104}, journal = {Biochemical and Biophysical Research Communications}, keywords = {Animals Cell_Line Hela_Cells Humans Neurotensin Protein_Interaction_Mapping Protein_Multimerization Protein_Structure Rats Receptors Tertiary}, month = jan, note = {{PMID:} 19968961}, number = 1, pages = {1007--1013}, timestamp = {2011-08-03T20:51:54.000+0200}, title = {Intermolecular cross-talk between {NTR1} and {NTR2} neurotensin receptor promotes intracellular sequestration and functional inhibition of {NTR1} receptors}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19968961}, volume = 391, year = 2010 }