Gustatory Receptors sense RNA and ribonucleic acid metabolites as nutrients and signaling molecules during rapid growth

味觉受体在快速生长过程中将 RNA 和核糖核酸代谢物感知为营养物质和信号分子

• 批准号: 9090249
• 负责人: Hubert O Amrein
• 金额: $ 18.56万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9090249
• 关键词: Adult; Afferent Neurons; Amino Acids; Animals; Area; Behavior; Behavioral; Behavioral Assay; Behavioral Genetics; Biological Assay; Biological Models; Biological Neural Networks; Biology; Brain; Carbohydrates; Cells; Chemicals; Code; Complex; DNA; Data; Detection; Development; Discrimination; Drosophila genus; Drosophila gustatory receptor; Drosophila melanogaster; Electrophysiology (science); Energy Metabolism; Fatty Acids; Food; Gene Family; Genes; Goals; Growth; Hunger; Image; Insect Proteins; Insecta; Intestines; Larva; Lead; Ligands; Light; Locomotion; Logic; Mammals; Mediating; Modality; Molecular; Molecular Genetics; Nematoda; Neurons; Nutrient; Perception; Phase; Play; Poison; Population; Process; Protein Family; Proteins; Public Health; Publications; RNA; RNA Precursors; Receptor Gene; Regulation; Reporting; Research; Ribose; Role; Satiation; Sensory; Sensory Process; Signaling Molecule; Source; Staging; System; Taste Buds; Taste Perception; Temperature Sense; Uridine; Work; base; detection of nutrient; feeding; fly; genetic analysis; interest; macromolecule; mutant; novel; nutrition; preference; programs; public health relevance; rapid growth; receptor; reproductive; research study; sensor; sensory system; sugar; taste system; tool

 DESCRIPTION (provided by applicant): The ability to identify different chemicals is a ubiquitous feature of most animals, from primitive roundworms to mammals. The most important feeding decisions animals have to make is to discriminate between palatable tasty food chemicals, such as sugars, and aversive, bitter tasting and possibly toxic chemicals. A second more elaborate process is the identification of food best suited for a specific condition, such as overall nutrition status (hunger vs. satiation), anticipated need for major energy expenditure (locomotion), a developmental stage or reproductive phase. To accommodate these needs, gustatory systems have evolved sensors for the identification of different types of nutrients. In this application, we will investigate the functions of a highly conserved Drosophila Gustatory receptor (Gr) gene subfamily in sensing biomolecules. Specifically, we present strong evidence that implicates the Gr28 gene family (Gr28a, Gr28b.a-b.e) in the perception of RNA through its ribose moiety. We show that Drosophila larvae are highly attracted to RNA/ribose, a preference entirely dependent on the presence of the Gr28 genes. Using a novel Ca2+ indicator (CaMPARI), we establish that RNA, ribose and uridine activate taste neurons expressing Gr28a. We also show that RNA, but not DNA is necessary for normal growth and survival during larval development. This is the first association of Gr genes with a direct chemosensory function in the detection of large biomolecules. We hypothesize that the Gr28 proteins recognize RNA precursor and other ribose containing compounds both externally and internally. Thus, this proposal will likely establish a molecular mechanism not only for the detection of exogenous RNA related nutrients, but also for the previously reported roles for these receptors in light and temperature sensing. Drosophila has been the major non-vertebrate model system in the study of taste sensory perception, as it provides a range of molecular genetic tools that can be employed in both cellular and whole animal assays, such as electrophysiological recordings and Ca2+ imaging on taste neurons and behavioral analyses. While the receptors (at least for sugar and bitter compounds) are evolutionarily not conserved between mammals and insects, the organization of the gustatory systems and the logic of taste coding in these diverse animal phyla are remarkably similar. Moreover, the use of taste receptors in postprandial nutrient sensing (either in the gut or the brain) has been reported in both systems, and likely plays important roles in feeding regulation. Thus, this work will have a significant impact on fundamental principles of conserved chemosensory processes.

 描述（由适用提供）：识别不同化学物质的能力是大多数动物的无处不在特征，从原始的round虫到哺乳动物。动物必须做出的最重要的喂养决定是区分可口的美味食品化学物质，例如糖，厌恶，苦味品尝和可能的有毒化学物质。第二个更详尽的过程是鉴定最适合特定条件的食物，例如总体营养状况（饥饿与满意度），预期对主要能量消耗的需求（运动），发育阶段或生殖阶段。为了满足这些需求，味道系统具有进化的传感器，以识别不同类型的养分。在此应用中，我们将研究高度组成的果蝇（GR）基因在感测生物分子中的功能。具体而言，我们提供了有力的证据，表明通过其核糖部分对RNA感知，实现了GR28基因家族（GR28A，GR28B.A-B.E）。我们表明，果蝇幼虫被RNA/核糖高度吸引，这完全取决于GR28基因的存在。使用新型的Ca2+指标（Campari），我们确定RNA，核糖和尿苷激活表达GR28A的味觉神经元。我们还表明，在幼虫发育过程中，RNA对于正常生长和生存是必需的。这是GR基因与直接化学强度功能的第一个关联。我们假设GR28蛋白在外部和内部识别含有化合物的RNA前体和其他核糖。这就是该建议可能不仅建立了一种分子机制，不仅用于检测外源性RNA相关的营养素，而且还可以为这些受体在光和温度感测方面的作用而建立一种分子机制。果蝇一直是味觉感知感知研究中的主要非魔力模型系统，因为它提供了一系列可用于细胞和整个动物测定中的分子遗传工具，例如电生理记录以及味觉神经元和行为分析的CA2+成像。虽然受体（至少用于糖和苦涩的化合物）在哺乳动物和昆虫之间并不保守，但在这些不同的动物门中，味觉系统的组织和味觉编码的逻辑非常相似。此外，在两种系统中都报道了味觉受体在餐后营养敏感性（无论是在肠道还是大脑中），并且可能在进食调节中起重要作用。这项工作将对保守化学感觉过程的基本原理产生重大影响。