TY - JOUR
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 - G protein-coupled receptors
KW - Receptor dimerization
KW - Resonance energy transfer
KW - Serotonin
KW - cAMP
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U2 - 10.1016/j.febslet.2005.04.040
DO - 10.1016/j.febslet.2005.04.040
M3 - Article
C2 - 15896782
AN - SCOPUS:20444416043
SN - 0014-5793
VL - 579
SP - 2973
EP - 2980
JO - FEBS Letters
JF - FEBS Letters
IS - 14
ER -