Elucidating the role of a renal proximal tubule‐specific olfactory receptor

Olfactory receptors (ORs) are seven transmembrane domain G protein‐coupled chemosensors 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 where they have important functions. We have previously reported that OR signaling plays a role in the kidney, and that Olfr1393 is present in the kidney (PNAS 2009). Using reverse‐transcribed RNA from microdissected renal segments, we found that Olfr1393 is exclusively expressed in all three segments of the proximal tubule (S1, S2 and S3, n=3). Olfr1393, like the majority of ORs, is an “orphan receptor” with no known ligand. To screen for ligands, Olfr1393 must first be expressed on the plasma membrane (PM). However, most ORs are retained in the ER when expressed in HEK293T cells. We have recently cloned this renal OR and found that it can traffic to the PM when coexpressed with Receptor Trafficking Protein. Using a comprehensive screening approach, we have found that Olfr1393 detects cyclic molecules containing a carbonyl group. There are a vast array of physiological chemicals that are derived from this basic unit including bile acids, vitamins and steroid hormones, all of which play important roles in the kidney. We are currently focusing on defining the full complement of ligands for Olfr1393, and understanding the physiological role that this OR plays in the kidney. Funding NIDDK