title: Formyl peptide receptors from immune and vomeronasal system exhibit distinct agonist properties.
abstract: The formyl peptide receptor (Fpr) family is well known for its contribution to immune defense against pathogens in human and rodent leukocytes. Recently, several structurally related members of these receptors were discovered in sensory neurons of the mouse vomeronasal organ (VNO), key detectors of pheromones and related semiochemicals. Although the biological role of vomeronasal Fprs is not yet clear, the known contribution of other Fprs to host immune defense suggested that they could contribute to vomeronasal pathogen sensing. Precise knowledge about the agonist properties of mouse Fprs is required to determine their function. We expressed all seven mouse and three human Fprs using an in vitro system and tested their activation with 32 selected compounds by conducting high throughput calcium measurements. We found an intriguing functional conservation between human and mouse immune Fprs that is most likely a consequence of closely similar biological constraints. By contrast, our data suggest a neofunctionalization of the vomeronasal Fprs. We show that the vomeronasal receptor mFpr-rs1 can be activated robustly by W-peptide and structural derivatives but not by other typical ligands of immune Fprs. mFpr-rs1 exhibits a stereo-selective preference for peptides containing d-amino acids. The same peptide motifs are contained in pathogenic microorganisms. Thus, the ligand profile of mFpr-rs1 is consistent with a role in vomeronasal pathogen sensing.
authors.affiliation: Department of Physiology, University of Saarland School of Medicine, 66421 Homburg, Germany. bernd.bufe@uks.eu
authors.forename: Bernd
authors.initials: B
authors.lastname: Bufe
authors.forename: Timo
authors.initials: T
authors.lastname: Schumann
authors.forename: Frank
authors.initials: F
authors.lastname: Zufall
mesh_terms: D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007107:Immune System / Q000502:physiology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010675:Pheromones; D044042:Receptors, Formyl Peptide / Q000737:chemistry*; D012903:Smell; D019147:Vomeronasal Organ / Q000502:physiology*
chemical_list: D017931:DNA Primers; D008024:Ligands; D010455:Peptides; D010675:Pheromones; D044042:Receptors, Formyl Peptide; D002118:Calcium