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Elucidating the Role of a Renal Proximal Tubule‐Specific Olfactory Receptor

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 cyclic molecules containing either a carbonyl or alcohol group. We also found that when transiently expressed in MDCK cells, Olfr1393 localizes to the apical, not the basolateral PM. To determine the function of this receptor, we generated knockout (KO) mice; the first KO pups were recently born, and they are viable with no overt phenotype. In conclusion, we have shown that Olfr1393 an apically localized, PT‐specific OR which responds to cyclic molecules. Future studies will examine PT function in wild‐type and KO mice to better understand the role that Olfr1393 plays in the kidney.