Intermolecular cross-talk between NTR1 and NTR2 neurotensin receptor promotes intracellular sequestration and functional inhibition of NTR1 receptors

Jae Ryoung Hwang; Min Woo Baek; Jeonggu Sim; Heung Sik Choi; Ji Man Han; You Lim Kim; Jong Ik Hwang; Hyuk Bang Kwon; Nicolas Beaudet; Philippe Sarret; Jae Young Seong

doi:10.1016/j.bbrc.2009.12.007

Intermolecular cross-talk between NTR1 and NTR2 neurotensin receptor promotes intracellular sequestration and functional inhibition of NTR1 receptors

Jae Ryoung Hwang, Min Woo Baek, Jeonggu Sim, Heung Sik Choi, Ji Man Han, You Lim Kim, Jong Ik Hwang, Hyuk Bang Kwon, Nicolas Beaudet, Philippe Sarret, Jae Young Seong

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1007-1013
Number of pages	7
Journal	Biochemical and biophysical research communications
Volume	391
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2009.12.007
Publication status	Published - 2010 Jan 1

Bibliographical note

Funding Information:
This work was supported by Grants from the Korea Research Foundation ( KRF-2006-005-J03001 ), the Ministry of Sciences and Technology ( R01-2004-000-10163-0 ), and the Canadian Institutes of Health Research ( CIHR, MOP-74618 ) awarded, respectively, to J.Y.S., H.B.K. and P.S. P.S. is a CIHR new investigator and member of the FRSQ-funded Centre de Recherche Clinique Étienne Lebel.

Keywords

Dimerization
G-protein-coupled receptor
Neurotensin
Signal transduction
Trafficking

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2009.12.007

Cite this

Hwang, J. R., Baek, M. W., Sim, J., Choi, H. S., Han, J. M., Kim, Y. L., Hwang, J. I., Kwon, H. B., Beaudet, N., Sarret, P., & Seong, J. Y. (2010). Intermolecular cross-talk between NTR1 and NTR2 neurotensin receptor promotes intracellular sequestration and functional inhibition of NTR1 receptors. Biochemical and biophysical research communications, 391(1), 1007-1013. https://doi.org/10.1016/j.bbrc.2009.12.007

Intermolecular cross-talk between NTR1 and NTR2 neurotensin receptor promotes intracellular sequestration and functional inhibition of NTR1 receptors. / Hwang, Jae Ryoung; Baek, Min Woo; Sim, Jeonggu et al.
In: Biochemical and biophysical research communications, Vol. 391, No. 1, 01.01.2010, p. 1007-1013.

Research output: Contribution to journal › Article › peer-review

Hwang, JR, Baek, MW, Sim, J, Choi, HS, Han, JM, Kim, YL, Hwang, JI, Kwon, HB, Beaudet, N, Sarret, P & Seong, JY 2010, 'Intermolecular cross-talk between NTR1 and NTR2 neurotensin receptor promotes intracellular sequestration and functional inhibition of NTR1 receptors', Biochemical and biophysical research communications, vol. 391, no. 1, pp. 1007-1013. https://doi.org/10.1016/j.bbrc.2009.12.007

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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.",

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AU - Choi, Heung Sik

AU - Han, Ji Man

AU - Kim, You Lim

AU - Hwang, Jong Ik

AU - Kwon, Hyuk Bang

AU - Beaudet, Nicolas

AU - Sarret, Philippe

AU - Seong, Jae Young

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N2 - 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.

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Intermolecular cross-talk between NTR1 and NTR2 neurotensin receptor promotes intracellular sequestration and functional inhibition of NTR1 receptors

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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