β-defensins and pigmentation
The melanocortin 1 receptor (Mc1r) plays a key role in regulating pigment-type switching in vertebrates, with its activation promoting synthesis of a dark pigment called eumelanin and its inhibition promoting synthesis of a lighter pigment called pheomelanin. Although much of the natural variation in mammalian coat color is explained by variant alleles of Mc1r or of Agouti, which encodes an inhibitory ligand for Mc1r, a recent mapping study in dogs identified another locus, termed K, with marked effects on pigmentation. Now, Greg Barsh and colleagues (Science, advance online publication 18 October 2007; doi:10.1126/science.1147880) show that the K locus encodes a member of the β-defensin family of antimicrobial peptides. The evidence, which includes genetic mapping and mutation analysis in dogs, transgenic studies in mice and biochemical assays in heterologous cell lines, suggests that the product of the K locus promotes eumelanin production by binding directly to Mc1r and acting as a competitive inhibitor of Agouti. This unexpected link between β-defensins and the melanocortin pathway highlights the utility of genetic mapping for revealing biological functions and suggests that diversity within the β-defensin gene family may have been driven, in part, by selection related to pigmentation. KV
This is a preview of subscription content, access via your institution
