AXOR12, a novel human G protein-coupled receptor, activated by the peptideKiSS-1

A novel human G protein-coupled receptor named AXOR12, exhibiting 81% homol ogy to the rat orphan receptor GPR54, was cloned from a human brain cDNA li brary. Heterologous expression of AXOR12 in mammalian cells permitted the i dentification of three surrogate agonist peptides, all with a common C-term inal amidated motif. High potency agonism, indicative of a cognate ligand, was evident from peptides derived from the gene KiSS-1, the expression of w hich prevents metastasis in melanoma cells. Quantitative reverse transcript ase-polymerase chain reaction was used to study the expression of AXOR12 an d KiSS-1 in a variety of tissues. The highest levels of expression of AXOR1 2 mRNA were observed in brain, pituitary gland, and placenta. The highest l evels of KiSS-1 gene expression were observed in placenta and brain. A poly clonal antibody raised to the C. terminus of AXOR12 was generated and used to show localization of the receptor to neurons in the cerebellum, cerebral cortex, and brainstem. The biological significance of these expression pat terns and the nature of the putative cognate ligand for AXOR12 are discusse d.