MOLECULAR MECHANISMS OF PHOTORECEPTOR FUNCTION

光感受器功能的分子机制

• 批准号: 6384871
• 负责人: Barry E Knox
• 金额: $ 18.91万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6384871
• 关键词: Xenopus; biological signal transduction; genetically modified animals; receptor expression; rhodopsin; visual photoreceptor; visual pigments

DESCRIPTION: (Verbatim from applicant's abstract): The long-term interests of this laboratory are the molecular mechanisms underlying the development and function of rods and cones. The questions are how expression of photoreceptor genes is regulated and how these cell-specific proteins contribute to the delivery of rod and cone phototransduction responses. We will combine molecular and cell biology, confocal microscopy, electrophysiology and microspectrophotometry in a novel and powerful transgenic system, Xenopus, focusing on the visual pigments. We will investigate: (1) molecular mechanisms underlying photoreceptor noise; 2) visual pigment properties underlying the dynamics of rod and cone response; and (3) regulatory regions in opsin genes underlying rod- and cone-specific expression. The rapid and inexpensive production of transgenic Xenopus, coupled with the large size of photoreceptors suitable for suction electrode recording, cone-rich retina and photoreceptor-specific promoters establish Xenopus as an ideal model for the proposed studies. The ability to introduce opsin mutants that have altered stability or photochemistry into rod cells will allow us to address several longstanding issues about rod photoreceptor behavior: mechanisms controlling sensitivity, noise and response recovery in a comprehensive way. Moreover, the characterization of promoters for opsins in cones opens the way to study cone physiology and signal transduction in an experimentally tractable organism. One of the principal determinants of visual system performance is photoreceptor sensitivity, which is limited by the inherent noise of the photoreceptor. In fact, noise plays an important role in dark adaptation and pathophysiological conditions such as night blindness and retinal degeneration. Given the importance of noise in determining visual sensitivity and the wide range of opsin mutants that impair vision, we intend to study the properties of rhodopsin that determine the lifetime of activated rhodopsin (equivalent to Meta II) which plays a crucial role in terminating the cell's response kinetics and amplification, in order to further understand the factors that limit daylight vision.

描述：（逐字研究申请人的摘要）： 该实验室是开发和 杆和锥的功能。问题是感光器的表达方式 基因受调节，以及这些细胞特异性蛋白如何促进 杆和锥光转导响应的递送。我们将结合分子 和细胞生物学，共聚焦显微镜，电生理学和 新颖而强大的转基因系统Xenopus中的微光照射法， 专注于视觉颜料。我们将研究：（1）分子机制 底层光感受器噪声； 2）视觉色素特性 杆和锥反应的动力学； （3）Opsin基因的调节区域 基础杆和锥体特异性表达。快速廉价的 转基因爪蟾的产生，再加上大尺寸的感光体 适用于吸气电极记录，富含锥体的视网膜和 光感受器特异性启动子将Xenopus建立为理想模型 拟议的研究。引入已改变的Opsin突变体的能力 稳定性或光化学对杆细胞的光化学将使我们能够解决几个 关于杆光感受器行为的长期问题：控制机制 敏感性，噪音和响应恢复以全面的方式恢复。而且， 锥体中蛋白酶的启动子的表征开辟了研究锥体的方式 实验可法生物体的生理和信号转导。 视觉系统性能的主要决定因素之一是感光器 灵敏度，受感光器的固有噪声的限制。在 事实，噪声在黑暗适应和病理生理中起重要作用 夜失明和视网膜变性等条件。鉴于 噪声在确定视觉灵敏度和广泛范围的重要性 损害视力的Opsin突变体，我们打算研究 视紫红质确定活化的视紫红质的寿命（相当于 元II）在终止细胞的响应动力学方面起着至关重要的作用 和放大，以进一步了解限制的因素 日光视觉。