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)

作者：McRobie Helen R^*; King Linda M; Fanutti Cristina; Symmons Martyn F; Coussons Peter J

来源：FEBS LETTERS, 2014, 588(14): 2335-2343.

DOI：10.1016/j.febslet.2014.05.032

• Melanocortin-1 receptor
• Agouti signalling protein
• Melanocyte stimulating hormone
• Sciurus carolinensis
• Grey squirrel
• Melanism

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 (MC1R Delta 24) variant. We demonstrate that the MC1R Delta 24 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 MC1R Delta 24. We conclude that the deletion in the MC1R Delta 24 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.

• 出版日期2014-6-27