Olfactory receptors (ORs) are seven transmembrane domain G protein-coupled chemosensory receptors that serve as sensors of smell in the nose. Recently, studies have found that ORs and other chemosensors are also expressed outside of their native tissues, including in sperm, muscle and the spinal column, where they have important functional roles. We have previously reported that OR signaling also plays a role in the kidney and are actively characterizing the physiological functions of individual renal ORs. To date, we have identified 9 renal ORs including Olfr1393 which is the subject of this proposal. Preliminary findings suggest that Olfr1393 is exclusively localized to the proximal tubule (segments S1, S2 and S3). The proximal tubule begins at the base of the glomerulus and extends to the Loop of Henle, thus, it is the first segment of the nephron to come in contact with the newly forming urine. Therefore, the proximal tubule has an active rate of transport and is responsible for the majority of renal solute reabsorption including salt, water, potassium, glucose and amino acids. In this proposal, we aim to understand the role that Olfr1393 plays in the proximal tubule by asking three major questions. First, what is the ligand(s) for Olfr1393? Second, what is the complete expression pattern of Olfr1393? Finally, what functional role does Olfr1393 and its ligand play in the kidney? Our considerable experience in the field of molecular biology, cell biology and renal physiology well-situates us to perform these exciting experiments. By uncovering the role of this novel signaling pathway in the proximal tubule and in renal function as a whole, we hope to uncover novel roles for ORs and better understand how the kidney maintains such tight regulation on homeostatic functions.
The lining of the kidney comes in contact with a diverse range of chemicals and it must carefully regulate the concentration of each one in the urine and in the blood. Recently, olfactory receptors (the receptors in your nose that govern your sense of smell) have been found in the kidney, and in this study we are studying the role of one of these receptors in helping the kidney to maintain the balance of various substances in the body. Uncovering the function of this receptor will shed light on how the kidney maintains tight regulation of the components of the urine and blood, and may provide novel therapeutic strategies for those suffering from renal failure.
|Shepard, Blythe D; Cheval, Lydie; Peterlin, Zita et al. (2016) A Renal Olfactory Receptor Aids in Kidney Glucose Handling. Sci Rep 6:35215|
|Shepard, Blythe D; Pluznick, Jennifer L (2016) How does your kidney smell? Emerging roles for olfactory receptors in renal function. Pediatr Nephrol 31:715-23|
|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|