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

 描述(申请人提供)：从原始蛔虫到哺乳动物，识别不同化学物质的能力是大多数动物普遍存在的特征。动物必须做出的最重要的喂养决定是区分可口的可口的食物化学物质，如糖，以及令人厌恶的苦味和可能的有毒化学物质。第二个更精细的过程是确定最适合特定条件的食物，如总体营养状况(饥饿与饱足)、主要能量消耗的预期需求(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传感器来识别不同类型的营养物质。在这个应用中，我们将研究高度保守的果蝇味觉受体(Gr)基因亚家族在感知生物分子中的功能。具体地说，我们提出了强有力的证据，表明Gr28基因家族(Gr28a，Gr28b.a-B.e)通过其核糖部分参与RNA的感知。我们发现果蝇幼虫高度吸引RNA/核糖，这一偏好完全取决于Gr28基因的存在。利用一种新的钙指示剂(Campari)，我们证实了RNA、核糖和尿苷激活了表达Gr28a的味觉神经元。我们还表明，在幼虫发育过程中，正常生长和存活所必需的是RNA，而不是DNA。这是Gr基因在检测大生物分子时第一次与直接化学传感功能相关联。我们假设Gr28蛋白在外部和内部都能识别RNA前体和其他含有核糖的化合物。因此，这一提议可能会建立一个分子机制，不仅用于检测外源RNA相关的营养物质，而且还用于先前报道的这些受体在光和温度传感中的作用。果蝇一直是研究味觉知觉的主要非脊椎动物模型系统，因为它提供了一系列分子遗传学工具，可以用于细胞和整个动物的分析，如味觉神经元的电生理记录和钙成像以及行为分析。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)在进化上不是保守的，但这些不同的动物门的味觉系统的组织和味觉编码的逻辑非常相似。此外，味觉感受器在餐后营养感知(无论是在肠道还是在大脑中)的使用在这两个系统中都有报道，并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传感过程的基本原理产生重大影响。

 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.