The Sensing Liver: Localization and Ligands

项目摘要 感觉受体是七个跨膜结构域G蛋白偶联的化学受体（GPCR），其支配 一个人对周围世界的感觉和解释。这些受体包括嗅觉受体 (ORs)味觉受体（TRs），视蛋白和其他未充分研究的感觉GPCR（GPRs）， 它们遍布全身，帮助调节各种生理功能。在K01资助的工作中 grant（DK106400），我们发现这些受体之一Olfr 1393在多种组织中表达 包括肾脏、肝脏和小肠，在小肠中它有助于调节葡萄糖重吸收， 糖尿病的进展。为了确定可能也调节代谢的其他感觉受体， 功能，我们使用qPCR基因表达阵列筛选了体内最大的代谢器官肝脏， 卡.到目前为止，我们已经发现了总共86种感觉受体在小鼠肝脏中表达，并且已经缩小了 13个“高表达”受体。这项补助金的目的是完全描述这些 受体。要做到这一点，我们必须了解它们在哪里被发现（在细胞和亚细胞水平）， 确定它们的配体分布从R03提案中获得的数据将发现有希望的新线索， 帮助我们确定这些感觉受体在健康和疾病中的功能。

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.