| Title: | Crucial role of copper in detection of metal-coordinating odorants |
| Author(s): | Duan X; Block E; Li Z; Connelly T; Zhang J; Huang Z; Su X; Pan Y; Wu L; Chi Q; Thomas S; Zhang S; Ma M; Matsunami H; Chen GQ; Zhuang H; |
| Address: | "Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai E-Institute for Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China" |
| ISSN/ISBN: | 1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking) |
| Abstract: | "Odorant receptors (ORs) in olfactory sensory neurons (OSNs) mediate detection of volatile odorants. Divalent sulfur compounds, such as thiols and thioethers, are extremely potent odorants. We identify a mouse OR, MOR244-3, robustly responding to (methylthio)methanethiol (MeSCH(2)SH; MTMT) in heterologous cells. Found specifically in male mouse urine, strong-smelling MTMT [human threshold 100 parts per billion (ppb)] is a semiochemical that attracts female mice. Nonadjacent thiol and thioether groups in MTMT suggest involvement of a chelated metal complex in MOR244-3 activation. Metal ion involvement in thiol-OR interactions was previously proposed, but whether these ions change thiol-mediated OR activation remained unknown. We show that copper ion among all metal ions tested is required for robust activation of MOR244-3 toward ppb levels of MTMT, structurally related sulfur compounds, and other metal-coordinating odorants (e.g., strong-smelling trans-cyclooctene) among >125 compounds tested. Copper chelator (tetraethylenepentamine, TEPA) addition abolishes the response of MOR244-3 to MTMT. Histidine 105, located in the third transmembrane domain near the extracellular side, is proposed to serve as a copper-coordinating residue mediating interaction with the MTMT-copper complex. Electrophysiological recordings of the OSNs in the septal organ, abundantly expressing MOR244-3, revealed neurons responding to MTMT. Addition of copper ion and chelator TEPA respectively enhanced and reduced the response of some MTMT-responding neurons, demonstrating the physiological relevance of copper ion in olfaction. In a behavioral context, an olfactory discrimination assay showed that mice injected with TEPA failed to discriminate MTMT. This report establishes the role of metal ions in mammalian odor detection by ORs" |
| Keywords: | "Amino Acid Sequence Animals Cations/pharmacology Chelating Agents/pharmacology Copper/*physiology Cyclic AMP/analysis Dose-Response Relationship, Drug Ethylenediamines/pharmacology Female Histidine/chemistry Humans Male Mice Mice, Inbred C57BL Models, Mol;" |
| Notes: | "MedlineDuan, Xufang Block, Eric Li, Zhen Connelly, Timothy Zhang, Jian Huang, Zhimin Su, Xubo Pan, Yi Wu, Lifang Chi, Qiuyi Thomas, Siji Zhang, Shaozhong Ma, Minghong Matsunami, Hiroaki Chen, Guo-Qiang Zhuang, Hanyi eng R01 DC005782/DC/NIDCD NIH HHS/ DC006213/DC/NIDCD NIH HHS/ R55 DC006213/DC/NIDCD NIH HHS/ DC005782/DC/NIDCD NIH HHS/ R01 DC010857/DC/NIDCD NIH HHS/ R01 DC006213/DC/NIDCD NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2012/02/14 Proc Natl Acad Sci U S A. 2012 Feb 28; 109(9):3492-7. doi: 10.1073/pnas.1111297109. Epub 2012 Feb 10" |
