Agouti signalling protein is an inverse agonist to the wildtype and agonist to the melanic variant of the melanocortin-1 receptor in the grey squirrel (Sciurus carolinensis) |
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| Authors: | Helen R. McRobie Linda M. King Cristina Fanutti Martyn F. Symmons Peter J. Coussons |
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| Affiliation: | 1. Department of Life Sciences, Anglia Ruskin University, OPT 028, East Road, Cambridge CB1 1PT, UK;2. University of East Anglia, UK;3. University of Cambridge, UK |
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| Abstract: | The melanocortin-1 receptor (MC1R) is a key regulator of mammalian pigmentation. Melanism in the grey squirrel is associated with an eight amino acid deletion in the mutant melanocortin-1 receptor with 24 base pair deletion (MC1RΔ24) variant. We demonstrate that the MC1RΔ24 exhibits a higher basal activity than the wildtype MC1R (MC1R-wt). We demonstrate that agouti signalling protein (ASIP) is an inverse agonist to the MC1R-wt but is an agonist to the MC1RΔ24. We conclude that the deletion in the MC1RΔ24 leads to a receptor with a high basal activity which is further activated by ASIP. This is the first report of ASIP acting as an agonist to MC1R. |
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| Keywords: | MC1R, melanocortin-1receptor MC1R-wt, melanocortin-1 receptor of the wildtype MC1RΔ24, mutant melanocortin-1 receptor with 24 base pair deletion ASIP, agouti signalling protein POMC, pro-opiomelanocortin CREB, cAMP responsive element binding protein TRP-1, tyrosinase-related protein DCT, dopachrome tautomerase α-MSH, alpha melanocyte stimulating hormone cAMP, cyclic adenosine monophosphate TM, transmembrane helix ECL, extracellular loop |
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