Down-Regulation of Melanocortin Receptor Signaling Mediated by the Amino Terminus of Agouti Protein in Xenopus Melanophores

The study investigated the role of the amino-terminal residues of Agouti protein in melanocortin receptor (Mcr) signaling using Xenopus melanophores. It was found that the full-length Agouti protein induced receptor down-regulation in a time- and temperature-dependent manner, a result not observed with the carboxyl-terminal fragment alone. This suggested that the amino terminus of Agouti protein is crucial for sustained inhibition of Mcr signaling. In contrast, the carboxyl-terminal fragment and Agouti-related protein (Agrp) acted solely as competitive antagonists. These findings highlighted the complex regulatory mechanisms of Mcr signaling by Agouti protein and Agrp, emphasizing the distinct role of the amino terminus in receptor down-regulation.