Olfactory Proteins in the Kidney and Regulation of Glomerular Filtration Rate

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DESCRIPTION (provided by applicant): Olfactory receptors (ORs) are seven-transmembrane chemosensors which are responsible for the initial step of odorant detection in the olfactory epithelium. Recently, ORs have also been found to play a role in chemosensation in non-olfactory tissues. However, a role of ORs as chemosensors in the kidney, and therefore as potential regulators of kidney function, has not previously been investigated. Preliminary data demonstrates that individual ORs, as well as the necessary downstream signaling components of olfaction (the olfactory G protein and the olfactory form of adenylate cyclase) are expressed in the kidney. Furthermore, a mouse deficient for the olfactory form of adenylate cyclase is unable to properly regulate the rate of glomerular filtration - a deficit we believe is due to inappropriate regulation of tubuloglomerular feedback. In this proposal, we will: (1) Localize ORs within the kidney, (2) Determine if the olfaction machinery plays a role in tubuloglomerular feedback, and (3) Determine the ligand(s) detected by renal ORs in vitro and in vivo. The candidate's goals are focused on understanding renal physiology and pathophysiology, and she intends to pursue an academic appointment in research. The Department of Cellular and Molecular Physiology at Yale University is an ideal environment in which to further cultivate the candidate's interest and expertise in renal physiology, and the Sponsor's Laboratory provides an excellent setting in which to investigate a novel renal signaling pathway.