TY - JOUR A1 - Behrens, Maik A1 - Frank, Oliver A1 - Rawel, Harshadrai Manilal A1 - Ahuja, Gaurav A1 - Potting, Christoph A1 - Hofmann, Thomas A1 - Meyerhof, Wolfgang A1 - Korsching, Sigrun T1 - ORA1, a Zebrafish Olfactory Receptor Ancestral to All Mammalian V1R Genes, Recognizes 4-Hydroxyphenylacetic Acid, a Putative Reproductive Pheromone JF - The journal of biological chemistry N2 - The teleost v1r-related ora genes are a small, highly conserved olfactory receptor gene family of only six genes, whose direct orthologues can be identified in lineages as far as that of cartilaginous fish. However, no ligands for fish olfactory receptor class A related genes (ORA) had been uncovered so far. Here we have deorphanized the ORA1 receptor using heterologous expression and calcium imaging. We report that zebrafish ORA1 recognizes with high specificity and sensitivity 4-hydroxyphenylacetic acid. The carboxyl group of this compound is required in a particular distance from the aromatic ring, whereas the hydroxyl group in the para-position is not essential, but strongly enhances the binding efficacy. Low concentrations of 4-hydroxyphenylacetic acid elicit increases in oviposition frequency in zebrafish mating pairs. This effect is abolished by naris closure. We hypothesize that 4-hydroxyphenylacetic acid might function as a pheromone for reproductive behavior in zebrafish. ORA1 is ancestral to mammalian V1Rs, and its putative function as pheromone receptor is reminiscent of the role of several mammalian V1Rs as pheromone receptors. Y1 - 2014 U6 - https://doi.org/10.1074/jbc.M114.573162 SN - 0021-9258 SN - 1083-351X VL - 289 IS - 28 SP - 19778 EP - 19788 PB - American Society for Biochemistry and Molecular Biology CY - Bethesda ER -