Mechanisms of Olfactory Transduction

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The sense of smell plays an increasingly appreciated role in our general quality of life and well being, a role that is compromised by the effect of disease, drugs, aging and environmental onslaught on our chemosensory competence. Receptor neurons in the nose serve the critical function of detecting and transducing odorants. Disruption of any of the intracellular events leading to receptor cell activation can result in olfactory dysfunction. Emerging evidence implicates phosphoinositide signaling and the transient receptor potential (TRP) ion channels commonly targeted by this signaling pathway in chemosensory transduction in taste receptor cells, vomeronasal receptor neurons, invertebrate olfactory receptor neurons, and possibly in vertebrate olfactory receptor neurons, where recent evidence suggests it can modulate the well established cyclic nucleotide signaling pathway. Phosphoinositide signaling is inherently complex, and this complexity has impeded a clear understanding of its role in many cellular systems. In this continuing project, we use an integrated, molecular, biochemical, and electrophysiologicalapproach to further define the cellular mechanisms of phosphoinositide signaling in an olfactory system. We use an animal model in which the functional role of phosphoinositide signaling in olfactory transduction is particularly well established, and has led to the evidence suggesting a potential role for phosphoinositide signaling in vertebrate olfaction. This project has the potential to identify new cellular and molecular events potentially involved in olfactory receptor cell activation, as well as contribute to a more general understanding of phospholipid signaling and TRP channel function in chemical sensing.