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.

Public Health Relevance

One of the most important aspects of kidney function is the kidney's ability to properly regulate and adjust the amount and rate of urine flow as well as to monitor the various components of urine;however, the details of this process are not fully understood. We have found that the same proteins in your nose which allow you to smell are also present in the cells in your kidney which are responsible for monitoring urine flow. In this proposal, we will investigate how these proteins help the kidney to sniff the urine as it flows by so that the amount, rate, and various components of urine can be carefully monitored and adjusted.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Rys-Sikora, Krystyna E
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Johns Hopkins University
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United States
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Peti-Peterdi, János; Kishore, Bellamkonda K; Pluznick, Jennifer L (2016) Regulation of Vascular and Renal Function by Metabolite Receptors. Annu Rev Physiol 78:391-414
Shepard, Blythe D; Cheval, Lydie; Peterlin, Zita et al. (2016) A Renal Olfactory Receptor Aids in Kidney Glucose Handling. Sci Rep 6:35215
Pluznick, Jennifer L (2014) Extra sensory perception: the role of Gpr receptors in the kidney. Curr Opin Nephrol Hypertens 23:507-12
Shepard, Blythe D; Natarajan, Niranjana; Protzko, Ryan J et al. (2013) A cleavable N-terminal signal peptide promotes widespread olfactory receptor surface expression in HEK293T cells. PLoS One 8:e68758
Pluznick, Jennifer L (2013) Renal and cardiovascular sensory receptors and blood pressure regulation. Am J Physiol Renal Physiol 305:F439-44
Pluznick, Jennifer L; Caplan, Michael J (2012) Novel sensory signaling systems in the kidney. Curr Opin Nephrol Hypertens 21:404-9
Pluznick, Jennifer L (2011) Beyond translation: the renal phosphate census. Focus on ""Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule"". Am J Physiol Cell Physiol 300:C752-4