Melanocortin receptors and antagonists regulate pigmentation and body weight.
The action two genetic loci--agouti and the melanocortin receptor-1 (Mc1r)-- have opposing effects in the control of mammalian pigmentation and ultimately determine the color of the pigment produced. In a recent paper, Ollmann et al. confirmed that the agouti protein acts via the Mc1r. They show that high-affinity binding of the agouti protein to Mc1r expressed in mammalian cells can be inhibited by the receptor's natural ligand, alpha-melanocyte-stimulating hormone (alpha-MSH). In addition, genetic studies using mice carrying mutations at the Mc1r and agouti loci on a sensitized background of low tyrosinase expression confirm that a functional Mc1r is required for the maximum pigmentary effect of agouti. Thus, the Mc1r appears to be a unique, bifunctionally controlled receptor, activated by alpha-MSH and antagonized by agouti, both of which contribute to the variability seen in mammalian coat color.
MRC Human Genetics Unit, Western General Hospital, Edinburgh, Scotland.
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D054366:Agouti Signaling Protein; D000818:Animals; D001835:Body Weight; D006200:Hair Color / Q000235:genetics* / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008322:Mammals; D051379:Mice; D008817:Mice, Mutant Strains; D011506:Proteins / Q000502:physiology*; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors / Q000502:physiology*; D044101:Receptors, Melanocortin; D000521:alpha-MSH / Q000037:antagonists & inhibitors / Q000502:physiology
D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C515183:a protein, mouse; D000521:alpha-MSH