Zebrafish olfactory receptors ORAs differentially detect bile acids and bile salts

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 rec...

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Bibliographic Details
Published in:The Journal of biological chemistry 2019-04, Vol.294 (17), p.6762-6771
Main Authors: Cong, Xiaojing, Zheng, Qian, Ren, Wenwen, Chéron, Jean-Baptiste, Fiorucci, Sébastien, Wen, Tieqiao, Zhang, Chunbo, Yu, Hongmeng, Golebiowski, Jérôme, Yu, Yiqun
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
behavioral assay
Bile Acids and Salts - metabolism
Biochemistry, Molecular Biology
Bioinformatics
Cell Biology
Chemical Sciences
Cheminformatics
Computer Science
Computer Simulation
fish ORA
homology modeling
Life Sciences
Ligands
molecular docking
molecular dynamics
Mutagenesis, Site-Directed
Neurons and Cognition
olfactory receptor
or physical chemistry
receptor structure–function
Receptors, Odorant - chemistry
Receptors, Odorant - genetics
Receptors, Odorant - metabolism
site-directed mutagenesis
Structure-Activity Relationship
Theoretical and
Zebrafish
Zebrafish Proteins - chemistry
Zebrafish Proteins - genetics
Zebrafish Proteins - metabolism
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.RA118.006483