RT Journal Article
T1 Molecular, biochemical and behavioural evidence for a novel oxytocin receptor and serotonin 2C receptor heterocomplex
A1 Chruścicka, Barbara
A1 Cowan, Caitlin S.M.
A1 Wallace Fitzsimons, Shauna E.
A1 Borroto Escuela, Dasiel Óscar
A1 Druelle, Clémentine M.
A1 Stamou, Panagiota
A1 Bergmann, Cristian A.
A1 Dinan, Timothy G.
A1 Slattery, David A.
A1 Fuxe, Kjell
A1 Cryan, John F.
A1 Schellekens, Harriët
K1 Receptores de hormonas
K1 Receptores celulares
K1 Oxitocina
K1 Serotonina
AB The complexity of oxytocin-mediated functions is strongly associated with its modulatory effects on other neurotransmission systems, including the serotonin (5-hydroxytryptamine, 5-HT) system. Signalling between oxytocin (OT) and 5-HT has been demonstrated during neurodevelopment and in the regulation of specific emotion-based behaviours. It is suggested that crosstalk between neurotransmitters is driven by interaction between their specific receptors, particularly the oxytocin receptor (OTR) and the 5-hydroxytryptamine 2C receptor (5-HTR2C), but evidence for this and the downstream signalling consequences that follow are lacking. Considering the overlapping central expression profiles and shared involvement of OTR and 5-HTR2C in certain endocrine functions and behaviours, including eating behaviour, social interaction and locomotor activity, we investigated the existence of functionally active OTR/5-HTR2C heterocomplexes. Here, we demonstrate evidence for a potential physical interaction between OTR and 5-HTR2C in vitro in a cellular expression system using flow cytometry-based FRET (fcFRET). We could recapitulate this finding under endogenous expression levels of both receptors via in silico analysis of single cell transcriptomic data and ex vivo proximity ligation assay (PLA). Next, we show that co-expression of the OTR/5-HTR2C pair resulted in a significant depletion of OTR-mediated Gαq-signalling and significant changes in receptor trafficking. Of note, attenuation of OTR-mediated downstream signalling was restored following pharmacological blockade of the 5-HTR2C. Finally, we demonstrated a functional relevance of this novel heterocomplex, in vivo, as 5-HTR2C antagonism increased OT-mediated hypoactivity in mice. Overall, we provide compelling evidence for the formation of functionally active OTR/5-HTR2C heterocomplexes, adding another level of complexity to OTR and 5-HTR2C signalling functionality.
PB Elsevier
SN 00283908
YR 2021
FD 2021-02-01
LK https://hdl.handle.net/10630/45034
UL https://hdl.handle.net/10630/45034
LA eng
NO Barbara Chruścicka, Caitlin S.M. Cowan, Shauna E. Wallace Fitzsimons, Dasiel O. Borroto-Escuela, Clémentine M. Druelle, Panagiota Stamou, Cristian A. Bergmann, Timothy G. Dinan, David A. Slattery, Kjell Fuxe, John F. Cryan, Harriët Schellekens, Molecular, biochemical and behavioural evidence for a novel oxytocin receptor and serotonin 2C receptor heterocomplex, Neuropharmacology, Volume 183, 2021, 108394, ISSN 0028-3908, https://doi.org/10.1016/j.neuropharm.2020.108394. (https://www.sciencedirect.com/science/article/pii/S0028390820304627)
NO Science Foundation Ireland (SFI)
NO National Science Centre (NCN, Poland)
NO Swedish Medical Research Council (Sweden / Vetenskapsrådet)
NO Hjärnfonden
NO Karolinska Institutet Forskningsstiftelser
NO Olle Engkvist Stiftelse
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 27 feb 2026