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-HT4(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 beta2-adrenergic receptor (beta2AR) 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.
authors.affiliation: Laboratoire de Cardiologie Cellulaire et Moléculaire, INSERM U-446, Châtenay-Malabry, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Berthouze
authors.forename: Mohammed
authors.initials: M
authors.lastname: Ayoub
authors.forename: Olivier
authors.initials: O
authors.lastname: Russo
authors.forename: Lucie
authors.initials: L
authors.lastname: Rivail
authors.forename: Sames
authors.initials: S
authors.lastname: Sicsic
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Fischmeister
authors.forename: Isabelle
authors.initials: I
authors.lastname: Berque-Bestel
authors.forename: Ralf
authors.initials: R
authors.lastname: Jockers
authors.forename: Frank
authors.initials: F
authors.lastname: Lezoualc'h
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D019281:Dimerization; D006801:Humans; D047468:Immunoprecipitation; D008024:Ligands; D008163:Luminescent Measurements; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D020033:Protein Isoforms; D011985:Receptors, Serotonin; C078730:serotonin 5 receptor