The Sensing Liver: Localization and Ligands

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Project Summary Sensory receptors are seven transmembrane domain G protein-coupled chemoreceptors (GPCRs) that govern one’s sensation and interpretation of their surrounding world. These receptors, that include olfactory receptors (ORs), taste receptors (TRs), opsins, and other understudied sensory GPCRs (GPRs), are expressed throughout the body where they help to regulate diverse physiological functions. In work funded by a K01 grant (DK106400), we found that one of these receptors, Olfr1393, is expressed in a variety of tissues including the kidney, liver, and small intestine where it contributes to the regulation of glucose reabsorption and the progression of diabetes. To identify additional sensory receptors that may also modulate metabolic function, we screened the liver, the largest metabolic organ in the body, using qPCR gene expression array cards. To date, we have found a total of 86 sensory receptors expressed in murine liver, and have narrowed down the list to 13 ‘highly expressed’ receptors. The aim of this grant is to completely characterize these receptors. To do so, we must understand where they are found (both at the cellular and subcellular level) and identify their ligand profile. The data acquired from this R03 proposal will uncover promising new leads that will assist us in determining the functions that these sensory receptors have in both health and disease.