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（由申请人提供）：识别不同化学物质的能力是大多数动物的普遍特征，从原始蛔虫到哺乳动物。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品，如糖，和令人厌恶的苦味和可能有毒的化学品。第二个更复杂的过程是识别最适合特定条件的食物，例如总体营养状况（饥饿与饱足）、预期的主要能量消耗需求（运动）、发育阶段或生殖阶段。为了适应这些需求，味觉系统已经进化出用于识别不同类型的营养素的传感器。 在本论文中，我们将研究一个高度保守的果蝇味觉受体（Gr）基因亚家族在感受生物分子中的功能。具体来说，我们提出了强有力的证据，暗示Gr 28基因家族（Gr 28 a，Gr 28 b.a-b.e）通过核糖部分感知RNA。我们发现，果蝇幼虫高度吸引RNA/核糖，偏好完全依赖于Gr 28基因的存在。使用一种新的Ca 2+指示剂（CaMPARI），我们建立了RNA，核糖和尿苷激活味觉神经元表达Gr 28 a。我们还表明，RNA，而不是DNA是必要的正常生长和生存在幼虫发育。这是Gr基因在检测大生物分子中首次与直接化学传感功能相关联。我们假设Gr 28蛋白质识别RNA前体和其他含有核糖的化合物的外部和内部。因此，这一建议将可能建立一个分子机制，不仅用于检测外源RNA相关的营养物质，而且还为以前报道的这些受体在光和温度传感中的作用。 果蝇一直是味觉感知研究中的主要非脊椎动物模型系统，因为它提供了一系列可用于细胞和整体动物测定的分子遗传工具，例如味觉神经元的电生理记录和Ca 2+成像以及行为分析。虽然哺乳动物和昆虫之间的受体（至少是糖和苦味化合物的受体）在进化上并不保守，但这些不同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，味觉受体在餐后营养感测（在肠道或大脑中）中的使用在两个系统中都有报道，并且可能在摄食调节中发挥重要作用。因此，这项工作将对保守的化学感受过程的基本原理产生重大影响。