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.

加密色素（哭泣）将紫外线和蓝色波长光转化为神经元膜的快速变化 通过基于氧化还原的机制通过 电压门控的K+通道β亚基表达功能性氧化还原传感器，该传感器将光线激活 哭到神经元膜的去极化。最近，我们发现Rhodopsin 7（RH7）是一个特级 视网膜视网膜蛋白也在腹侧神经元中表达并将紫罗兰色的光转化为去极化和 神经元发射率提高。光激活的RH7伴侣伴随着多种G蛋白途径。因此，我们有 在中央脑神经元中发现了两种新型的光转传。哭泣和RH7 在外侧神经元中相互作用，该神经元从外部接收第三个光学输入 感受器。这就提出了基于氧化还原的哭声与A之间的信号交互的新问题 G蛋白偶联的OPSIN在同一神经元中，以及光驱动突触输入的进一步调节。 使用基于强大的分子遗传学以及行为分析和生理学的综合方法， 我们发现在蝇神经元中表达的哭声调节了紫外线照相和其他轻驱动行为，包括 执行选择。我们最近的工作表明，这些发出复杂光的信号传导机制 响应行为对昼夜节时间的影响高度敏感，甚至昼夜偏好也是如此。 哭泣与RH7之间的相互作用提供了苍蝇的精确时间信息，我们可以监视这些信息 通过单细胞分辨率的昼夜节律整个电路成像。机会很大，因为 迄今 由于蚊子仅限于基于视网膜的Opsin的光转导。我们建议确定这些 短波长光转导系统会收敛到少数神经元以驱动光反应 以及苍蝇和蚊子的一天中的行为。我们的研究提供了改善光线的新机会 通过了解新型氧化还原和基于G蛋白的光信号传导的基本生物学来控制昆虫 机制。