Formyl peptide receptor-like receptors: an olfactory tool to identify pathogens?
Final Report Abstract
Most mammals rely heavily on conspecific chemical communication mechanisms to interact adequately with each other. They utilize different types of seven-transmembrane G protein– coupled receptors to identify both general odorants and pheromones. Using a mouse model, we and others recently discovered that members of the formyl peptide receptor (FPR) family are exclusively expressed in sensory neurons of the vomeronasal organ. We identified agonists for these receptors, and observed that most of these FPR ligands are linked to pathogens and / or pathogenic states. Moreover, we demonstrated that subpopulations of vomeronasal neurons do respond to these agonists. Based on these exciting findings, we proposed a project to investigate a) the characteristics of genetically engineered VSNs expressing a defined FPR receptor, b) the physiological properties of these neurons and the transduction cascade triggered downstream FPR activation, and c) the functional role of the vomeronasal system in the discrimination of unhealthy individuals in mice. In the course of the funded project, we generated transgenic mice in which VSNs expressing Fpr-rs3 could be visualized in vivo via the expression of a genetically-encoded fluorophore. We also provided a detailed description of the physiological properties of these neurons. So far, however, we have not been able to report a full profile of the molecular receptive spectrum of FPR-rs3. We encountered several difficulties when testing activation of labeled neurons in slices and / or isolated preparations. However, we are confident that we will be able to provide more information on FPR-rs3 signaling in the future. Finally, we evaluated the potential role played by the vomeronasal system in sick conspecific avoidance. We evaluated two different "pathogenic states", used two independent ways to alter vomeronasal function, and developed assays to monitor the aversion of healthy mice towards unhealthy conspecifics or bodily fluids produced by sick conspecifics. We found that these chemical signals linked to sickness activate vomeronasal neurons and that impairment of vomeronasal function abolish preference towards healthy individuals.
Publications
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(2013) Convergence of FPR-rs3- expressing neurons in the mouse accessory olfactory bulb. Mol. Cell. Neurosci. 56C:140–147
Dietschi Q, Assens A, Challet L, Carleton A, Rodriguez I
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(2014) Physiological characterization of formyl peptide receptor expressing cells in the mouse vomeronasal organ. Front. Neuroanat. 8: 134
Ackels T, von der Weid B, Rodriguez I, Spehr M
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(2015) The Vomeronasal System Mediates Sick Conspecific Avoidance. Current Biology 25: 251-255
Boillat M, Challet L, Rossier D, Kan C, Carleton A, Rodriguez I
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(2016) In-depth physiological analysis of defined cell populations in acute tissue slices of the mouse vomeronasal organ. J Vis Exp. 2016 Sep 10;(115)
Ackels T, Drose DR, Spehr M
