UV to blue neuronal phototransduction mechanisms

紫外到蓝色神经元光转导机制

• 批准号: 9900018
• 负责人: Todd C Holmes
• 金额: $ 42.28万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900018
• 关键词: Arousal; Behavior; Behavioral; Biology; Brain; Cells; Complex; Coupled; Couples; Cues; Culicidae; Drosophila genus; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; Image; Insect Control; Insecta; Invertebrates; Lateral; Light; Membrane; Membrane Potentials; Molecular Genetics; Monitor; Mosquito Control; Neurons; Opsin; Oxidation-Reduction; Pathway interactions; Photoreceptors; Phototransduction; Physiology; Reaction Time; Research; Resolution; Retina; Rhodopsin; Signal Transduction; Sleep; Synapses; System; Time; Viola; Voltage-Gated Potassium Channel; Work; base; behavioral response; circadian; cryptochrome; fly; improved; novel; preference; sensor; ultraviolet

Cryptochrome (CRY) transduces ultraviolet and blue wavelength light to rapid changes in neuronal membrane potential of lateral ventral circadian/arousal neurons in Drosophila brains by a redox based mechanism via voltage-gated K+ channel beta subunits that express a functional redox sensor that couples light activated CRY to depolarization of the neuronal membrane. Recently, we found that Rhodopsin 7 (Rh7) is an extra- retinal opsin that also expresses in the lateral ventral neurons and transduces violet light to depolarization and increased neuronal firing rate. Light activated Rh7 couples to multiple G-protein pathways. Thus, we have contributed to the discovery of two novel phototransduction that occur in central brain neurons. CRY and Rh7 interact in the lateral ventral neurons, which receive a third photic input synaptically from external photoreceptors. This raises a new set of questions of signaling interactions between redox-based CRY and a G protein-coupled opsin in the same neurons along with further modulation from light driven synaptic inputs. Using an integrative approach based on powerful molecular genetics and behavioral analysis and physiology, we find that CRY expressed in fly neurons regulates UV phototaxis and other light driven behaviors including executive choice. Our most recent work shows that these signaling mechanisms that drive complex light response behaviors are highly sensitive to circadian time of day effects, even diurnal vs. nocturnal preferences. The interactions between CRY and Rh7 provide precise time-of-day information to flies, which we can monitor by circadian whole circuit imaging at single cell resolution. The opportunities are enormous because heretofore, our understanding of short wavelength light sensing in invertebrates, including harmful insects such as mosquitoes has been limited to retinal opsin-based phototransduction. We propose to determine how these short wavelength phototransduction systems converge to a small number of neurons to drive light responses and time of day behavior in flies and mosquitoes. Our research provides new opportunities to improve light control of insects by understanding the fundamental biology of novel redox and G-protein based light signaling mechanisms.

隐花色素（CRY）可将紫外光和蓝光转换为神经元膜的快速变化 通过氧化还原为基础的机制，果蝇脑中侧腹侧昼夜节律/唤醒神经元的电位 电压门控K+通道β亚基，表达一种功能性氧化还原传感器， CRY对神经元膜的去极化。最近，我们发现视紫红质7（Rh 7）是一种额外的- 视网膜视蛋白，也在侧腹神经元中表达，并将紫光转换为去极化， 增加神经元放电率。光激活的Rh 7与多个G蛋白途径偶联。因此，我们有 这两个新的光转导发生在中枢脑神经元的发现作出了贡献。CRY和Rh 7 在侧腹神经元中相互作用，侧腹神经元从外部突触接收第三光输入。 光感受器这就提出了一系列新的问题，即基于氧化还原的CRY和蛋白质之间的信号相互作用。 G蛋白偶联的视蛋白在相同的神经元中沿着来自光驱动的突触输入的进一步调制。 使用基于强大的分子遗传学和行为分析和生理学的综合方法， 我们发现，在果蝇神经元中表达的CRY调节UV趋光性和其他光驱动行为，包括 行政选择。我们最近的工作表明，这些驱动复杂光的信号机制 反应行为对昼夜节律的时间效应高度敏感，甚至是昼夜相对于夜间的偏好。 CRY和Rh 7之间的相互作用为苍蝇提供了精确的时间信息，我们可以监测这些信息。 通过单细胞分辨率的昼夜全回路成像。机会是巨大的，因为 迄今为止，我们对无脊椎动物（包括有害昆虫， 因为蚊子局限于视网膜视蛋白基光转导。我们建议确定这些 短波长光转导系统会聚到少量神经元以驱动光响应 以及苍蝇和蚊子在一天中的时间行为。我们的研究提供了新的机会，以改善光 通过了解新型氧化还原和G蛋白光信号的基础生物学来控制昆虫 机制等