Unraveling the polymodal behavior of sensory transduction receptors

 描述(申请人提供)：动物可以探测多种刺激，包括化学物质、力、光和温度。不同的感觉模式往往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。这种多态现象是如何出现的？如何对其进行监管，以实现感官歧视？我们将通过研究我们在果蝇黑腹果蝇中发现的两类多模式受体来探索这些问题，果蝇的多模式受互补的分子机制调节。我们建议从三个方面来调查这些问题。1)我们将探索以细胞特异性的方式调节受体对温和温暖和厌恶化学物质的活性以获得适当的敏感性和特异性的分子机制，并利用这些研究来研究在果蝇和按蚊中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调节温度感觉和湿感觉，以及这些不同的活动如何被调节，以赋予果蝇和按蚊对每种刺激的适当行为反应。3)我们将测试多个相关受体可以以组合方式共同发挥作用的假设，以创建不同类别的感觉受体，在果蝇和按蚊的不同感觉神经元中介导对不同感觉形式的反应。总之，这些研究将为以下方面提供基本的见解：感觉受体多模式的分子基础，感觉受体如何检测温度和化学刺激，以及如何调节感觉受体的活动以实现适当的感觉敏感性和特异性。

 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.