Heterodimerization and interaction of the serotonin receptors 5-HT1A and 5-HT2C

G-Protein coupled receptors (GPCRs) are among the most prominent receptors in the central nervous system. Their malfunction is implicated in various neurological and neuropsychiatric disorders, making them a common target for medical treatment. Thus, it is crucial to gain a comprehensive understanding of GPCR functions and mechanisms to develop more effective and targeted medical treatments with fewer side effects.This study examines the potential interplay between the serotonin receptors 5-HT1A and 5-HT2C, which play a significant role in the pathology of depression. Experiments were performed in transfected HEK-293 cells expressing both receptors.Our findings provide initial evidence of heterodimerization between the 5-HT1A and 5-HT2C receptors, as indicated by FRET in acceptor photobleaching measurements. A significant increase in fluorescence intensity of the CFP-tagged 5-HT2C receptor of approximately 10% was observed after bleaching of the YFP-tagged 5-HT1A receptor. Further analysis of potential heterodimerization involves FLIM and Co-Immunoprecipitation/Western-Blot techniques.Additionally, calcium imaging experiments demonstrated significant signals in HEK-293 cells transfected with both receptors and GCaMP8 when exposed to serotonin.The potential interaction between the 5-HT1A and 5-HT2C receptors is further investigated by Patch-Clamp experiments.