Renal Olfactory Receptor 90: ligands, localization and function

肾嗅觉受体 90：配体、定位和功能

• 批准号: 9117978
• 负责人: Victoria Halperin Kuhns
• 金额: $ 4.36万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9117978
• 关键词: Adenylate Cyclase; Apical; Area; Aspergillus; Bacteria; Biological Assay; Blood; Breathing; CRISPR/Cas technology; Cell Line; Cell membrane; Cell surface; Cellular biology; Chemicals; Chemoreceptors; Chemotaxis; Cleaved cell; Creatinine; Data; Defect; Detection; Exposure to; G-Protein-Coupled Receptors; Glomerular Filtration Rate; Homeostasis; Human; Immunocompromised Host; In Situ Hybridization; In Vitro; Individual; Kidney; Knockout Mice; Length; Ligand Binding; Ligands; Macula densa; Measures; Mediating; Microbe; Molecular Biology; Monitor; Mus; Muscle; Mycoses; N-terminal; Nose; Olfactory Epithelium; Orphan; Orthologous Gene; Pathway interactions; Patients; Phenotype; Physiological; Physiology; Plasma; Play; Process; Proteins; Publishing; Receptor Signaling; Regulation; Renal function; Renin; Reporting; Role; Sensory Receptors; Signal Pathway; Signal Transduction; Smell Perception; Source; Surface; System; Urine; Work; apical membrane; base; experience; follow-up; fungus; immunocytochemistry; in vivo; microbiota; migration; novel; olfactory receptor; public health relevance; receptor; sensor; sperm cell; trafficking

 DESCRIPTION (provided by applicant): In recent years, olfactory receptors (ORs) have been shown to play a variety of important roles outside of the nose, acting as chemosensors to aid in muscle migration, sperm chemotaxis, and metabolite sensing. In 2009, we identified several ORs which are expressed in the kidney, including the topic of this proposal: Olfr90. We have recently deorphanized Olfr90, and found that it senses chemicals which have been reported to be present in blood and urine. However, these chemicals are not produced by the host - rather, they are metabolites produced by fungi. Recent studies by both our group and others have shown that there are at least three receptors for bacterial metabolites which play important roles in modulating physiological parameters in the host; however, few studies have examined a role for fungal metabolites in vertebrate physiology. In this proposal, we will follow up on this intriguing finding by working to better understand the role of Olfr90 in the kidney by: (I) Further characterizing the ligands to which Olfr90 responds and their physiological relevance, (II) Localizing Olfr90 within the kidney, and (III) Examining the phenotype of Olfr90 knockout mice both at baseline and after exposure to fungal sources. Our considerable experience in molecular biology, cell biology, and renal physiology, including previous work deorphanizing ORs and studying host-microbe interactions, makes us well-suited to explore this exciting new area. Through our studies of this novel signaling pathway, we hope to expand our understanding of host-microbe interactions and to uncover novel roles for ORs in renal physiology.

 描述（由适用提供）：近年来，嗅觉受体（OR）已被证明在鼻子外发挥了各种重要作用，充当化学传感器，可帮助肌肉迁移，精子趋化性和代谢物敏感性。 2009年，我们确定了几个在肾脏中表达的OR，包括该提案的主题：OLFR90。我们最近已脱足化的OLFR90，发现它感觉到据报道存在于血液和尿液中的化学物质。但是，这些化学物质不是由宿主产生的 - 而是它们是由真菌产生的代谢物。我们小组和其他人的最新研究表明，细菌代谢产物至少有三个受体在调节宿主的生理参数中起着重要作用。但是，很少有研究检查真菌代谢产物在脊椎动物生理学中的作用。在此提案中，我们将通过努力更好地了解OLFR90在肾脏中的作用来跟进这一有趣的发现：（i）进一步 （ii）在肾脏中定位OLFR90反应及其物理相关性的配体，以及（iii）在基线和暴露于真菌来源后检查OLFR90敲除小鼠的表型。我们在分子生物学，细胞生物学和肾脏生理学方面的考虑经验，包括以前的工作去畸形和研究宿主 - 微叶相互作用，使我们非常适合探索这个令人兴奋的新领域。通过我们对这一新型信号通路的研究，我们希望扩大我们对宿主 - 微生物相互作用的理解，并发现ORS在肾脏生理学中的新作用。