| Title: | Two highly related odorant receptors specifically detect alpha-bile acid pheromones in sea lamprey (Petromyzon marinus) |
| Author(s): | Zhang Z; Zhang Q; Dexheimer TS; Ren J; Neubig RR; Li W; |
| Address: | "Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai, China; International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China; Shanghai Universities Key Laboratory of Marine Animal Taxonomy and Evolution, Shanghai Ocean University, Shanghai, China. Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA. Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA. Electronic address: liweim@msu.edu. Department of Fisheries and Wildlife, Michigan State University, East Lansing, Michigan, USA. Electronic address: RNeubig@msu.edu" |
| ISSN/ISBN: | 1083-351X (Electronic) 0021-9258 (Print) 0021-9258 (Linking) |
| Abstract: | "Pheromones play critical roles in habitat identification and reproductive behavior synchronization in the sea lamprey (Petromyzon marinus). The bile acid 3-keto petromyzonol sulfate (3kPZS) is a major component of the sex pheromone mixture from male sea lamprey that induces specific olfactory and behavioral responses in conspecific individuals. Olfactory receptors interact directly with pheromones, which is the first step in their detection, but identifying the cognate receptors of specific pheromones is often challenging. Here, we deorphanized two highly related odorant receptors (ORs), OR320a and OR320b, of P. marinus that respond to 3kPZS. In a heterologous expression system coupled to a cAMP-responsive CRE-luciferase, OR320a and OR320b specifically responded to C(24) 5alpha-bile acids, and both receptors were activated by the same set of 3kPZS analogs. OR320a displayed larger responses to all 3kPZS analogs than did OR320b. This difference appeared to be largely determined by a single amino acid residue, Cys-79(2.56), the C-terminal sixth residue relative to the most conserved residue in the second transmembrane domain (2.56) of OR320a. This region of TM2 residues 2.56-2.60 apparently is critical for the detection of steroid compounds by odorant receptors in lamprey, zebrafish, and humans. Finally, we identified OR320 orthologs in Japanese lamprey (Lethenteron camtschaticum), suggesting that the OR320 family may be widely present in lamprey species and that OR320 may be under purifying selection. Our results provide a system to examine the origin of olfactory steroid detection in vertebrates and to define a highly conserved molecular mechanism for steroid-ligand detection by G protein-coupled receptors" |
| Keywords: | "Animals *Cholic Acids/chemistry/pharmacology *Fish Proteins/biosynthesis/chemistry/genetics *Lampreys/genetics/metabolism *Pheromones/chemistry/pharmacology *Receptors, Odorant/biosynthesis/chemistry/genetics G protein-coupled receptor (GPCR) agnathan bil;" |
| Notes: | "MedlineZhang, Zhe Zhang, Qinghua Dexheimer, Thomas S Ren, Jianfeng Neubig, Richard R Li, Weiming eng Research Support, Non-U.S. Gov't 2020/07/09 J Biol Chem. 2020 Aug 21; 295(34):12153-12166. doi: 10.1074/jbc.RA119.011532. Epub 2020 Jul 7" |
