Table 1.
Homo- and heterodimerization of the GHS-R1a receptor.
| Dimer | Physical interaction in vitro | Cell lines | Physical interaction in/ex vivo | Functional interaction in vivo | References |
|---|---|---|---|---|---|
| GHS-R1a/GHS-R1a | Binding and signal transduction assays demonstrate allosteric modulation of ghrelin signaling: calcium mobilization, inositol phosphate turnover, CRE and SRE transcription assay, β-arrestin mobilization, BRET, co-IP | Hek, COS-7 | nd | nd | Holst et al., 2005; Leung et al., 2007 |
| GHS-R1a/GHS-R1b | Subcellular co-localization using immunocytochemistry; BRET; ghrelin binding assay; cell surface expression ELISA; receptor downstream signaling; co-IP | Hek, CHO | nd | nd | Chan and Cheng, 2004; Chu et al., 2007; Leung et al., 2007; Chow et al., 2012; Mary et al., 2013 |
| GHS-R1a/EP3-1 | Co-IP; BRET | Hek | nd | nd | Chow et al., 2008 |
| GHS-R1a/IP | Co-IP; BRET | Hek | nd | nd | Chow et al., 2008 |
| GHS-R1a/TPα | Co-IP; BRET | Hek | nd | nd | Chow et al., 2008 |
| GHS-R1a/SST5 | Glucose-stimulated insulin secretion assay; tr-FRET; BRET; downstream Gq (calcium assay) and Gs (cAMP) signaling | Hek, INS-1SJ | nd | nd | Park et al., 2012 |
| GHS-R1b/NTS1 | Co-IP; Co-localization and receptor trafficking | Cos-7, LC319 | nd | nd | Takahashi et al., 2006 |
| GHS-R1a/MC3 | FRET; ELISA; Co-localization; binding assay; receptor trafficking and downstream Gq (NFAT-luciferase reporter or calcium assay) and Gs (cAMP) signaling | Hek, COS-7 | Co-expression of MC3 with lacZ-immunoreactive cells, representing GHS-R1a in Arc of GHS-R1a knock-out mice | nd | Rediger et al., 2009, 2011; Schellekens et al., 2013b |
| GHS-R1a/D1 | Co-IP; Co-localization; BRET; receptor trafficking and downstream Gq (calcium assay) and Gs (cAMP) signaling | Hek, SK-N-SH | Co-expression of D1 with GHS-R1a in the VTA of GHSR-IRES-tauGFP knock-in homozygous mice | nd | Jiang et al., 2006; Schellekens et al., 2013b |
| GHS-R1a/D2 | Co-localization; downstream signaling Gq and Gβγ subunit of Gi (calcium mobilization assay and imaging); tr-FRET | Hek, SH-SY5Y, Primary hypothalamic neurons | Co-expression of D2/GHS-R1a in hippocampus, striatum and hypothalamus of GHSR-IRES-tauGFP knock-in homozygous mice; Tr-FRET of striatum and hypothalamic tissue in wt and GHSR−/− mice | Allosteric function for GHS-R1a on D2-mediated inhibition of food intake. D2 agonist cabergoline reduces food intake in mice, which is absent when GHS-R1a is pharmacologically blocked or knocked out in GHS-R1a−/− mice | Kern et al., 2012 |
| GHS-R1a/5-HT2C | Co-localization; receptor trafficking and downstream Gq (calcium assay) signaling | Hek | nd | nd | Schellekens et al., 2013b |
Abbreviations: BRET, bioluminescence resonance energy transfer; co-IP, co-immunoprecipitation; CRE, cAMP-responsive element; ELISA, Enzyme-linked immunosorbent assay; D1/2, dopamine receptor 1/2; GHS-R, growth hormone secretagogue receptor; IP, prostaglandin (prostacyclin) receptor; EP, prostanoid receptor; MC3, melanocortin receptor 3; nd, not done; NFAT, nuclear factor of activated T cells; NTS1, neurotensin 1 receptor; SRE, serum-responsive element; TPα, thromboxane A2; tr-FRET, time-resolved fluorescence resonance energy transfer.