Dual activities of odorants on olfactory and nuclear hormone receptors

Pick, H. and Etter, S. and Baud, O. and Schmauder, R. and Bordoli, L. and Schwede, T. and Vogel, H.. (2009) Dual activities of odorants on olfactory and nuclear hormone receptors. Journal of biological chemistry, Vol. 284, H. 44. pp. 30547-30555.

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Official URL: http://edoc.unibas.ch/dok/A5259329

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We have screened an odorant compound library and discovered molecules acting as chemical signals which specifically activate both G protein-coupled olfactory receptors (OR) on the cell surface of olfactory sensory neurons and the human nuclear estrogen receptor alpha (ER) involved in transcriptional regulation of cellular differentiation and proliferation in a wide variety of tissues. Hence, these apparent dual active odorants induce distinct signal transduction pathways at different subcellular localizations which affect both neuronal signaling, resulting in odor perception, and the ER-dependent transcriptional control of specific genes. We demonstrate these effects using fluorescence-based in-vitro and cellular assays. Among these odorants, we have identified synthetic sandalwood compounds, an important class of molecules used in the fragrance industry. For one estrogenic odorant we have also identified the cognate OR. This prompted us to compare basic molecular recognition principles of odorants on the two structurally and apparent functionally non-related receptors using computational modeling in combination with functional assays. Faced with the increasing evidence that ORs may perform chemosensory functions in a number of tissues outside of the nasal olfactory epithelium, the unravelling of these molecular ligand-receptor interaction principles is of critical importance. In addition the evidence that certain olfactory sensory neurons naturally co-express ORs and ERs may provide a direct functional link between the olfactory and hormonal systems in humans. Our results are therefore useful for defining the structural and functional characteristics of ER-specific odorants and the role of odorant molecules in cellular processes other than olfaction.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Schwede)
UniBasel Contributors:Schwede, Torsten
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society of Biological Chemists
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:21
Deposited On:22 Mar 2012 13:22

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