title: 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).
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.
authors.affiliation: Department of Life Sciences, Anglia Ruskin University, OPT 028, East Road, Cambridge CB1 1PT, UK. Electronic address: helen.mcrobie@anglia.ac.uk.
authors.forename: Helen R
authors.initials: HR
authors.lastname: McRobie
authors.affiliation: Department of Life Sciences, Anglia Ruskin University, OPT 028, East Road, Cambridge CB1 1PT, UK. Electronic address: linda.king@anglia.ac.uk.
authors.forename: Linda M
authors.initials: LM
authors.lastname: King
authors.affiliation: University of East Anglia, UK. Electronic address: c.fanutti@uea.ac.uk.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fanutti
authors.affiliation: University of Cambridge, UK. Electronic address: mfs1001@cam.ac.uk.
authors.forename: Martyn F
authors.initials: MF
authors.lastname: Symmons
authors.affiliation: Department of Life Sciences, Anglia Ruskin University, OPT 028, East Road, Cambridge CB1 1PT, UK. Electronic address: peter.coussons@anglia.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Coussons
mesh_terms: D054366:Agouti Signaling Protein / Q000502:physiology*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D044102:Receptor, Melanocortin, Type 1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012589:Sciuridae; D015290:Second Messenger Systems; D017384:Sequence Deletion
chemical_list: D054366:Agouti Signaling Protein; D044102:Receptor, Melanocortin, Type 1; D000242:Cyclic AMP
keywords: Agouti signalling protein; Grey squirrel; Melanism; Melanocortin-1 receptor; Melanocyte stimulating hormone; Sciurus carolinensis