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Zebrafish olfactory receptors ORAs differentially detect bile acids and bile salts
- Zebrafish olfactory receptors ORAs differentially detect bile acids and bile salts
- Cong, Xiaojing; Zheng, Qian; Ren, Wenwen; Cheron, Jean-Baptiste; Fiorucci, Sebastien; Wen, Tieqiao; Zhang, Chunbo; Yu, Hongmeng; Golebiowski, Jerome; Yu, Yiqun
- Issue Date
- Journal of Biological Chemistry, 294(17), 6762-6771
- Article Type
- Author Keyword
- site-directed mutagenesis; receptor structure-function; molecular docking; molecular dynamics; homology modeling; behavioral assay; fish ORA; olfactory receptor
- Biochemistry; Fish; Life cycle; Mammals; Pattern recognition; Salts; Chemosensory receptors; Heterologous cells; Ligand recognition; Lithocholic acids; Olfactory receptors; Olfactory systems; Site directed mutagenesis; Structure-function relationship; Body fluids
- The fish olfactory receptor ORA family is orthologous to the mammalian vomeronasal receptors type 1. It consists of six highly conserved chemosensory receptors expected to be essential for survival and communication. We deorphanized the zebrafish ORA family in a heterologous cell system. The six receptors responded specifically to lithocholic acid (LCA) and closely related C24 5β-bile acids/salts. LCA attracted zebrafish as strongly as food in behavioral tests, whereas the less potent cholanic acid elicited weaker attraction, consistent with the in vitro results. The ORA-ligand recognition patterns were probed with site-directed mutagenesis guided by in silico modeling.We revealed the receptors' structure-function relationship underlying their specificity and selectivity for these compounds. Bile acids/salts are putative fish semiochemicals or pheromones sensed by the olfactory system with high specificity. This work identified their receptors and provided the basis for probing the roles of ORAs and bile acids/salts in fish chemosensation. © 2019 Cong et al.
- American Society for Biochemistry and Molecular Biology Inc.
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- ETC1. Journal Articles
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