Unraveling the polymodal behavior of sensory transduction receptors

揭示感觉转导受体的多模式行为

• 批准号: 9225161
• 负责人: Paul Garrity
• 金额: $ 45.58万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-15 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9225161
• 关键词: Adult; Affect; Afferent Neurons; Alpha Cell; Alternative Splicing; Animals; Anopheles Genus; Anopheles gambiae; Basic Science; Behavior; Chemicals; Child; Clustered Regularly Interspaced Short Palindromic Repeats; Culicidae; Data; Dengue; Detection; Development; Disease; Disease Vectors; Drosophila genus; Drosophila melanogaster; Esthesia; Family; G-Protein-Coupled Receptors; Genes; Health; Homeostasis; Humidity; Insect Vectors; Insecta; Light; Malaria; Mediating; Mediator of activation protein; Modality; Molecular; Molecular Probes; Neurons; Nociceptors; Physiology; Property; Protein Isoforms; RNA Splicing; Regulation; Role; Sensitivity and Specificity; Sensory; Sensory Receptors; Specific qualifier value; Specificity; Stimulus; TRPA1 Channel; Temperature; Temperature Sense; Testing; To specify; Work; behavioral response; combinatorial; experimental study; fly; gene function; genome editing; human disease; in vivo; insect disease; insight; interest; killings; member; mutant; novel; promoter; public health relevance; receptor; response; sensory discrimination; vector control; water vapor

 DESCRIPTION (provided by applicant): Animals detect multiple kinds of stimuli, including chemicals, force, light and temperature. Distinct sensory modalities often rely on related molecular receptors2. In some cases the same receptor participates in multiple sensory modalities. How does such polymodality emerge? How can it be regulated to enable sensory discrimination? We will probe these issues by studying two classes of polymodal receptors we have identified in the fruit fly Drosophila melanogaster whose polymodality is regulated by complementary molecular mechanisms. We propose to investigate these issues in three aims. 1) We will probe the molecular mechanisms by which the activity of a receptor for both moderate warming and aversive chemicals can be regulated in a cell-specific fashion to achieve appropriate sensitivity and specificity, and use these studies to investigate the molecular basis of thermal and chemical detection in both fruit flies and Anopheles mosquitoes. 2) We will investigate how a pair of receptors act together to mediate both thermosensation and hygrosensation, and how these distinct activities are regulated to confer appropriate behavioral responses to each stimulus in both fruit flies and Anopheles mosquitoes. 3) We will test the hypothesis that multiple related receptors can function together in a combinatorial fashion to create distinct classes of sensory receptors that mediate responses to distinct sensory modalities in different sensory neurons in both fruit flies and Anopheles mosquitoes. Together, these studies will provide fundamental insights into the molecular basis of sensory receptor polymodality, how sensory receptors detect thermal and chemical stimuli, and how sensory receptor activity can be regulated to achieve appropriate sensory sensitivity and specificity.

 描述（由申请人提供）：动物检测多种刺激，包括化学品、力、光和温度。不同的感觉方式通常依赖于相关的分子受体2。在某些情况下，同一受体参与多种感觉方式。这种多模态是如何出现的？如何调节它以实现感官辨别？我们将探讨这些问题，通过研究两类多模态受体，我们已经确定在果蝇黑腹果蝇的多模态是由互补的分子机制。我们建议在三个目标调查这些问题。1)我们将探讨的分子机制，通过该受体的活动，为温和的温暖和厌恶的化学物质可以调节在一个细胞特异性的方式，以实现适当的灵敏度和特异性，并利用这些研究来调查果蝇和按蚊的热和化学检测的分子基础。2)我们将研究一对受体如何共同作用来介导温度感觉和湿度感觉，以及如何调节这些不同的活动，以赋予果蝇和按蚊对每个刺激的适当行为反应。3)我们将测试的假设，多个相关的受体可以在一起发挥作用，以组合的方式来创建不同类别的感觉受体，介导不同的感觉神经元在果蝇和按蚊不同的感觉方式的反应。总之，这些研究将提供基本的见解感觉受体多模态的分子基础，感觉受体如何检测热和化学刺激，以及如何调节感觉受体的活动，以实现适当的感觉灵敏度和特异性。