Renal Olfactory Receptor 1393: Ligands, Localization and Function

肾嗅觉受体 1393：配体、定位和功能

• 批准号: 8511352
• 负责人: Blythe D Shepard
• 金额: $ 5.22万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8511352
• 关键词: Active Sites; Adenylate Cyclase; Amino Acids; Antibodies; Biological Assay; Blood; Brush Border; Calcium; Cellular biology; Chemicals; Coupled; Custom; Defect; Equilibrium; GTP-Binding Proteins; Galactosidase; Glomerular Filtration Rate; Glucose; Goals; Henle' s loop; Homeostasis; Individual; Ion Transport; Kidney; Kidney Failure; Life; Ligands; Light; Luciferases; Mitochondria; Molecular Biology; Monitor; Mus; Muscle; Nephrons; Nose; Olfactory Epithelium; Orphan; Pathway interactions; Pattern; Physiological; Physiology; Plasma; Play; Potassium; Process; Proximal Kidney Tubules; Receptor Signaling; Regulation; Renal function; Renin; Reporter; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Role; Signal Pathway; Signal Transduction; Smell Perception; Sodium Chloride; Staining method; Stains; Tissues; Transmembrane Domain; Urine; Vertebral column; Water; apical membrane; base; experience; mouse genome; novel; novel therapeutics; olfactory receptor; receptor; receptor function; research study; sensor; solute; sperm cell

DESCRIPTION (provided by applicant): Olfactory receptors (ORs) are seven transmembrane domain G protein-coupled chemosensory receptors 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, including in sperm, muscle and the spinal column, where they have important functional roles. We have previously reported that OR signaling also plays a role in the kidney and are actively characterizing the physiological functions of individual renal ORs. To date, we have identified 9 renal ORs including Olfr1393 which is the subject of this proposal. Preliminary findings suggest that Olfr1393 is exclusively localized to the proximal tubule (segments S1, S2 and S3). The proximal tubule begins at the base of the glomerulus and extends to the Loop of Henle, thus, it is the first segment of the nephron to come in contact with the newly forming urine. Therefore, the proximal tubule has an active rate of transport and is responsible for the majority of renal solute reabsorption including salt, water, potassium, glucose and amino acids. In this proposal, we aim to understand the role that Olfr1393 plays in the proximal tubule by asking three major questions. First, what is the ligand(s) for Olfr1393? Second, what is the complete expression pattern of Olfr1393? Finally, what functional role does Olfr1393 and its ligand play in the kidney? Our considerable experience in the field of molecular biology, cell biology and renal physiology well-situates us to perform these exciting experiments. By uncovering the role of this novel signaling pathway in the proximal tubule and in renal function as a whole, we hope to uncover novel roles for ORs and better understand how the kidney maintains such tight regulation on homeostatic functions.

描述（由申请人提供）：嗅觉受体（ORs）是7个跨膜结构域G蛋白偶联的化学感受受体，用作鼻子中的嗅觉传感器。最近，研究发现OR和其他化学传感器也在其天然组织外表达，包括精子，肌肉和脊柱，在那里它们具有重要的功能作用。我们以前曾报道过OR信号也在肾脏中发挥作用，并积极表征个体肾脏OR的生理功能。到目前为止，我们已经确定了9个肾脏OR，包括本提案的主题Olfr 1393。初步研究结果表明，Olfr 1393只定位于近端小管（S1，S2和S3段）。近端小管起始于肾小球的基部并延伸至亨利袢，因此，它是肾单位与新形成的尿液接触的第一段。因此，近端小管具有活跃的转运速率，并且负责大部分肾脏溶质重吸收，包括盐、水、钾、葡萄糖和氨基酸。在这个提议中，我们的目标是通过提出三个主要问题来了解Olfr 1393在近端小管中发挥的作用。首先，Olfr 1393的配体是什么？第二，Olfr 1393的完整表达模式是什么？最后，Olfr 1393及其配体在肾脏中发挥什么功能作用？我们在分子生物学、细胞生物学和肾脏生理学领域的丰富经验使我们能够进行这些令人兴奋的实验。通过揭示这种新的信号通路在近端小管和整个肾功能中的作用，我们希望揭示OR的新作用，并更好地了解肾脏如何保持对稳态功能的紧密调节。