November 2015

November 2015: Co-expression of the central “hunger” receptor, ghrelin, also called growth hormone secretagogue receptor (green) and the serotonin 2C (5HT2C) receptor (red) in a culture of human embryonic kidney cells.

Submitted by: Dr Harriet Schellekens

Dr. Harriët Schellekens is a Lecturer in the department of Anatomy & Neuroscience and a Principal Investigator with APC Microbiome Institute and Food for Health Ireland. Her research focusses on the neuronal circuitry underlying the complex relationship between stress, mood and food intake. In particular, her work involves the pharmacological targeting of G-protein coupled receptors (GPCRs) expressed in the brain. Recently, she has identified a novel heterodimer between two key GPCRs important in the central regulation of feeding behaviour, namely, the ghrelin or GHS-R1a receptor and the 5-HT2C receptor (Schellekens et al., JBC, 2013; Schellekens et al., ACS Chemical Neuroscience, 2015). These findings have uncovered a novel mechanism of serotonin-mediated attenuation of the ghrelin receptor, which is poised to have significant impact on the future pharmacological targeting of the ghrelin receptor in the homeostatic regulation of body weight as well as hedonic appetite signalling, which both play a significant role in the development of obesity.

The image depicts human embryonic kidney (Hek) cells with stable expression of the ghrelin receptor (green). Cells also express the 5HT2C receptor (red) after lentiviral transduction. Co-localized receptor expression and possible heterodimerization is indicated by yellow colour overlap. Cell nuclei were stained with bisbenzamide (blue). The image was taken using confocal microscopy.

Further reading:

Schellekens, H., De Francesco, P.N., Kandil, D., Theeuwes, W.F., McCarthy, T., van Oeffelen, W.E.P.A., Perelló, M., Giblin, L., Dinan, T.G., Cryan, J.C., Ghrelin’s orexigenic effect is modulated via 1 a serotonin 2C receptor interaction, ACS Chemical Neuroscience, 2015.

Schellekens, H., van Oeffelen, W.E.P.A., Dinan, T.G., Cryan, J.F., Promiscuous Dimerization of the Growth Hormone Secretagogue Receptor (GHS-R1a) Attenuates Ghrelin-mediated Signaling. J Biol Chem, 2013. Jan; 288(1): 181-91.