Bradykinin B2 and dopamine D2 receptors form a functional dimer

Publication date: Available online 27 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Anna Niewiarowska-Sendo, Agnieszka Polit, Monika Piwowar, Magdalena Tworzydło, Andrzej Kozik, Ibeth Guevara-Lora
In recent years a wide range of studies have shown that G protein-coupled receptors modulate a variety of cell functions through the formation of dimers. For instance, there is growing evidence for the dimerization of bradykinin or dopamine receptors, both as homodimers and heterodimers. A discovery of direct interactions of angiotensin II receptors with bradykinin 2 receptor (B2R) or dopamine D2 (D2R) receptor has led to a hypothesis on a potential dimerization between two latter receptors. In this study, we have demonstrated a constitutive colocalization of receptors on the membranes of HEK293 cells transiently transfected with plasmid vectors encoding B2R and D2R, fused with fluorescent proteins. The receptor colocalization was significantly enhanced by specific agonists of B2R or D2R after five minutes following the addition, whereas simultaneous stimulation with these agonists did not influence the B2R/D2R colocalization level. In addition, B2R-D2R heterodimerization was confirmed with FLIM-FRET technique. The most characteristic signaling pathways for B2R and D2R, dependent on intracellular Ca²⁺ and cAMP concentration, respectively, were analyzed in cells presenting similar endogenous expression of B2R and D2R. Significant changes in receptors' signaling were observed after simultaneous stimulation with agonists, suggesting significant transformations in proteins' conformation after dimerization. The evidence of B2R–D2R dimerization may open new perspectives in the modulation of diverse cellular functions which depend on their activation.

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