SIGNAL TRANSDUCTION BY G PROTEINS IN THE RETINAL

描述(摘自申请者的摘要)：吞噬和液体 视网膜色素上皮(RPE)的运输是 视觉处理和光感受器的存活。长期的 这项拟议研究的目的是了解分子调控。 这些过程中。申请人已经鉴定出一种新的G蛋白- 上皮神经肽受体偶联受体(ENPR)。ITS序列 与神经肽受体关系最密切，尤其是对 神经肽Y。编码ENPR的转录本存在于RPE和 睫状体；它们不存在于其他组织中，除了 大脑的一部分。这种受限的表达模式表明，ENPR 控制着一条独特的G蛋白偶联通路，对专门化的 RPE的功能。申请人提议履行职能 新型受体ENPR的特性研究 配体激活调节RPE吞噬和液体的假说 运输。这些研究将包括 人类基因，细胞和亚细胞定位的分析， 鉴定天然配基、G蛋白伙伴和第二个 信使。ENPR受体功能及信号转导的研究进展 通路可能有助于更好地理解ENPR是如何激活的 转化为正常所需的RPE的生理反应 光感受器的功能。

DESCRIPTION (Adapted from applicant's abstract): Phagocytosis and fluid transport in the retinal pigment epithelium (RPE) are necessary for visual processing and survival of the photoreceptors. The long-term goal of this proposed study is to understand the molecular regulation of these processes. The applicant has identified a novel G protein- coupled receptor, epithelium neuropeptide receptor (ENPR). Its sequence is most closely related to neuropeptide receptors, especially that for neuropeptide Y. Transcripts encoding ENPR are present in the RPE and ciliary body; they are not present in other tissues, with the exception of the brain. This restricted pattern of expression suggests that ENPR controls a unique G protein-coupled pathway important to the specialized functions of the RPE. The applicant proposes to perform functional characterization of the novel receptor ENPR in order to the test the hypothesis that ligand activation regulates RPE phagocytosis and fluid transport. These studies will include structural characterization of the human gene, analysis of cellular and subcellular localization, identification of the native ligand, G-protein partners, and second messengers. The elucidation of ENPR receptor function and signaling pathways may allow better understanding of how ENPR activation is translated into physiological responses of the RPE required for normal functioning of the photoreceptors.