Constitutive dimerization of human serotonin 5-HT4 receptors in living cells

Magali Berthouze; Mohammed Ayoub; Olivier Russo; Lucie Rivail; Sames Sicsic; Rodolphe Fischmeister; Isabelle Berque-Bestel; Ralf Jockers; Frank Lezoualc'h

doi:10.1016/j.febslet.2005.04.040

Constitutive dimerization of human serotonin 5-HT₄ receptors in living cells

Magali Berthouze, Mohammed Ayoub, Olivier Russo, Lucie Rivail, Sames Sicsic, Rodolphe Fischmeister, Isabelle Berque-Bestel, Ralf Jockers, Frank Lezoualc'h

Biological Sciences

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

61 Scopus citations

Abstract

Serotonin 5-HT₄ receptor isoforms are G protein-coupled receptors (GPCRs) with distinct pharmacological properties and may represent a valuable target for the treatment of many human disorders. Here, we have explored the process of dimerization of human 5-HT₄ receptor (h5-HT₄R) by means of co-immunoprecipitation and bioluminescence resonance energy transfer (BRET). Constitutive h5-HT_4(d)R dimer was observed in living cells and membrane preparation of CHO and HEK293 cells. 5-HT₄R ligands did not influence the constitutive energy transfer of the h5-HT_4(d)R splice variant in intact cells and isolated plasma membranes. In addition, we found that h5-HT_4(d)R and h5-HT _4(g)R which structurally differ in the length of their C-terminal tails were able to form constitutive heterodimers independently of their activation state. Finally, we found that coexpression of h5-HT₄R and β₂-adrenergic receptor (β₂AR) led to their heterodimerization. Given the large number of h5-HT₄R isoforms which are coexpressed in a same tissue, our results points out the complexity by which this 5-HTR sub-type mediates its biological effects.

Original language	British English
Pages (from-to)	2973-2980
Number of pages	8
Journal	FEBS Letters
Volume	579
Issue number	14
DOIs	https://doi.org/10.1016/j.febslet.2005.04.040
State	Published - 6 Jun 2005

Keywords

Bioluminescence
cAMP
G protein-coupled receptors
Receptor dimerization
Resonance energy transfer
Serotonin

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10.1016/j.febslet.2005.04.040

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title = "Constitutive dimerization of human serotonin 5-HT4 receptors in living cells",

abstract = "Serotonin 5-HT4 receptor isoforms are G protein-coupled receptors (GPCRs) with distinct pharmacological properties and may represent a valuable target for the treatment of many human disorders. Here, we have explored the process of dimerization of human 5-HT4 receptor (h5-HT4R) by means of co-immunoprecipitation and bioluminescence resonance energy transfer (BRET). Constitutive h5-HT4(d)R dimer was observed in living cells and membrane preparation of CHO and HEK293 cells. 5-HT4R ligands did not influence the constitutive energy transfer of the h5-HT4(d)R splice variant in intact cells and isolated plasma membranes. In addition, we found that h5-HT4(d)R and h5-HT 4(g)R which structurally differ in the length of their C-terminal tails were able to form constitutive heterodimers independently of their activation state. Finally, we found that coexpression of h5-HT4R and β2-adrenergic receptor (β2AR) led to their heterodimerization. Given the large number of h5-HT4R isoforms which are coexpressed in a same tissue, our results points out the complexity by which this 5-HTR sub-type mediates its biological effects.",

keywords = "Bioluminescence, cAMP, G protein-coupled receptors, Receptor dimerization, Resonance energy transfer, Serotonin",

author = "Magali Berthouze and Mohammed Ayoub and Olivier Russo and Lucie Rivail and Sames Sicsic and Rodolphe Fischmeister and Isabelle Berque-Bestel and Ralf Jockers and Frank Lezoualc'h",

note = "Funding Information: We thank Monique Gastineau for her excellent technical assistance. This work was supported by pre-doctoral grants from the Minist{\`e}re de la Recherche et de l{\textquoteright}Enseignement Sup{\'e}rieur (M.B, O.R, L.R).",

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T1 - Constitutive dimerization of human serotonin 5-HT4 receptors in living cells

AU - Berthouze, Magali

AU - Ayoub, Mohammed

AU - Russo, Olivier

AU - Rivail, Lucie

AU - Sicsic, Sames

AU - Fischmeister, Rodolphe

AU - Berque-Bestel, Isabelle

AU - Jockers, Ralf

AU - Lezoualc'h, Frank

N1 - Funding Information: We thank Monique Gastineau for her excellent technical assistance. This work was supported by pre-doctoral grants from the Ministère de la Recherche et de l’Enseignement Supérieur (M.B, O.R, L.R).

PY - 2005/6/6

Y1 - 2005/6/6

N2 - Serotonin 5-HT4 receptor isoforms are G protein-coupled receptors (GPCRs) with distinct pharmacological properties and may represent a valuable target for the treatment of many human disorders. Here, we have explored the process of dimerization of human 5-HT4 receptor (h5-HT4R) by means of co-immunoprecipitation and bioluminescence resonance energy transfer (BRET). Constitutive h5-HT4(d)R dimer was observed in living cells and membrane preparation of CHO and HEK293 cells. 5-HT4R ligands did not influence the constitutive energy transfer of the h5-HT4(d)R splice variant in intact cells and isolated plasma membranes. In addition, we found that h5-HT4(d)R and h5-HT 4(g)R which structurally differ in the length of their C-terminal tails were able to form constitutive heterodimers independently of their activation state. Finally, we found that coexpression of h5-HT4R and β2-adrenergic receptor (β2AR) led to their heterodimerization. Given the large number of h5-HT4R isoforms which are coexpressed in a same tissue, our results points out the complexity by which this 5-HTR sub-type mediates its biological effects.

AB - Serotonin 5-HT4 receptor isoforms are G protein-coupled receptors (GPCRs) with distinct pharmacological properties and may represent a valuable target for the treatment of many human disorders. Here, we have explored the process of dimerization of human 5-HT4 receptor (h5-HT4R) by means of co-immunoprecipitation and bioluminescence resonance energy transfer (BRET). Constitutive h5-HT4(d)R dimer was observed in living cells and membrane preparation of CHO and HEK293 cells. 5-HT4R ligands did not influence the constitutive energy transfer of the h5-HT4(d)R splice variant in intact cells and isolated plasma membranes. In addition, we found that h5-HT4(d)R and h5-HT 4(g)R which structurally differ in the length of their C-terminal tails were able to form constitutive heterodimers independently of their activation state. Finally, we found that coexpression of h5-HT4R and β2-adrenergic receptor (β2AR) led to their heterodimerization. Given the large number of h5-HT4R isoforms which are coexpressed in a same tissue, our results points out the complexity by which this 5-HTR sub-type mediates its biological effects.

KW - Bioluminescence

KW - cAMP

KW - G protein-coupled receptors

KW - Receptor dimerization

KW - Resonance energy transfer

KW - Serotonin

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JO - FEBS Letters

JF - FEBS Letters

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ER -

Constitutive dimerization of human serotonin 5-HT₄ receptors in living cells

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