Elucidating the role of a renal proximal tubule‐specific olfactory receptor (892.42)

Abstract

Olfactory receptors (ORs) are seven transmembrane domain G protein‐coupled chemosensors that detect odorants in the nose. We previously reported that OR signaling plays a role in the kidney (PNAS 2009), and to date we have identified 9 renal ORs. One of these is Olfr1393, which is widely expressed in a number of tissues, including kidney (by RT‐PCR screen). Using reverse‐transcribed RNA from microdissected renal segments, we found that Olfr1393 is exclusively expressed in the proximal tubule (PT; S1, S2 and S3). Like the majority of ORs, Olfr1393 is an orphan receptor with no known ligand. To screen for ligands, we cloned this receptor from the kidney and expressed it in HEK293T cells after optimizing conditions to allow for surface expression. We comprehensively screened over 1400 chemicals, and found that Olfr1393 detects preconstrained cyclic molecules containing either a carbonyl or alcohol group. We also found that when stably expressed in polarized MDCK cells, Olfr1393 localizes to the apical PM yet is excluded from the primary cilia. To determine the function of this receptor, we generated knockout (KO) mice. At baseline, KO mice appear to be in homeostatic balance based on plasma electrolytes, BUN, creatinine, urinalysis, and blood pressure measurements ‐ in future studies, we will challenge WT and KO mice with Olfr1393 ligands to ascertain how PT and renal function are regulated by Olfr1393.Grant Funding Source: Supported by: NIDDK and ASN