Title: | Zebrafish olfactory receptors ORAs differentially detect bile acids and bile salts |
Author(s): | Cong X; Zheng Q; Ren W; Cheron JB; Fiorucci S; Wen T; Zhang C; Yu H; Golebiowski J; Yu Y; |
Address: | "Universite Cote d'Azur, CNRS, Institut de Chimie de Nice UMR7272, Nice 06108 France. From the School of Life Sciences, Shanghai University, Shanghai 200444 China. Institutes of Biomedical Sciences, Fudan University, Shanghai 200031 China, and. Department of Biological and Chemical Sciences, Illinois Institute of Technology, Chicago, Illinois 60616. Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Fudan University, Shanghai 200031 China, hongmengyush@fudan.edu.cn. Universite Cote d'Azur, CNRS, Institut de Chimie de Nice UMR7272, Nice 06108 France, jerome.golebiowski@unice.fr. Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873 South Korea. From the School of Life Sciences, Shanghai University, Shanghai 200444 China, yiqun_yu@shu.edu.cn. Department of Otolaryngology, Eye, Ear, Nose and Throat Hospital, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Fudan University, Shanghai 200031 China" |
ISSN/ISBN: | 1083-351X (Electronic) 0021-9258 (Print) 0021-9258 (Linking) |
Abstract: | "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 C(24) 5beta-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" |
Keywords: | "Amino Acid Sequence Animals Bile Acids and Salts/*metabolism Computer Simulation Ligands Mutagenesis, Site-Directed Receptors, Odorant/chemistry/genetics/*metabolism Structure-Activity Relationship Zebrafish Zebrafish Proteins/chemistry/genetics/*metaboli;" |
Notes: | "MedlineCong, Xiaojing Zheng, Qian Ren, Wenwen Cheron, Jean-Baptiste Fiorucci, Sebastien Wen, Tieqiao Zhang, Chunbo Yu, Hongmeng Golebiowski, Jerome Yu, Yiqun eng R15 DC011650/DC/NIDCD NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2019/03/06 J Biol Chem. 2019 Apr 26; 294(17):6762-6771. doi: 10.1074/jbc.RA118.006483. Epub 2019 Mar 4" |