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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Transition Award (R00)
Project #
5R00DK081610-04
Application #
8121468
Study Section
Special Emphasis Panel (NSS)
Program Officer
Rys-Sikora, Krystyna E
Project Start
2008-07-28
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
4
Fiscal Year
2011
Total Cost
$246,510
Indirect Cost
Name
Johns Hopkins University
Department
Physiology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Kondapalli, Kalyan C; Todd Alexander, R; Pluznick, Jennifer L et al. (2017) NHA2 is expressed in distal nephron and regulated by dietary sodium. J Physiol Biochem 73:199-205
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 (2014) A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes 5:202-7
Pluznick, Jennifer L (2014) Extra sensory perception: the role of Gpr receptors in the kidney. Curr Opin Nephrol Hypertens 23:507-12
Rajkumar, Premraj; Aisenberg, William H; Acres, Omar W et al. (2014) Identification and characterization of novel renal sensory receptors. PLoS One 9:e111053
Pluznick, Jennifer L; Protzko, Ryan J; Gevorgyan, Haykanush et al. (2013) Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci U S A 110:4410-5
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

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