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
Career Transition Award (K99)
Project #
5K99DK081610-02
Application #
7666211
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2008-07-28
Project End
2010-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
2
Fiscal Year
2009
Total Cost
$88,354
Indirect Cost
Name
Yale University
Department
Physiology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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
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
Pluznick, Jennifer L; Rodriguez-Gil, Diego J; Hull, Michael et al. (2011) Renal cystic disease proteins play critical roles in the organization of the olfactory epithelium. PLoS One 6:e19694