Understanding Photoreceptor Trafficking Pathways to the Outer Segment

了解光感受器外段运输途径

• 批准号: 9892591
• 负责人: Jillian Nydam Pearring
• 金额: $ 2.66万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892591
• 关键词: Affect; Biochemistry; Cell membrane; Cells; Cellular biology; Cilia; Communities; Degenerative Disorder; Destinations; Development; Disease; Inherited; Light; Maintenance; Membrane; Membrane Proteins; Molecular Genetics; Neurobiology; Organelles; Pathway interactions; Patients; Photoreceptors; Positioning Attribute; Process; Proteins; Research; Research Personnel; Retina; Retinal; Retinal Degeneration; Retinal Diseases; Retinitis Pigmentosa; Signal Transduction; Signaling Protein; Structural Protein; Structure; Transplantation; Vision; ciliopathy; neuronal cell body; novel therapeutic intervention; photoreceptor cell outer segment; protein distribution; protein structure; stem cell technology; trafficking

PROJECT SUMMARY The first step of vision takes place in the retina where light is captured by the outer segment of photoreceptor cells. This light-sensing organelle is a modified primary cilium with a unique architechture (hundreds of tightly stacked disc membranes enclosed by a plasma membrane) that contains an elite set of signaling and structural proteins. Since proteins are synthesized in the cell soma they require discrete intracellular trafficking mechanisms to be delivered to the outer segment. These trafficking mechanisms are critical for development and general maintenance of photoreceptors, as the outer segment is a dynamic structure that must be continuously renewed. Understanding mechanisms governing subcellular distribution of proteins remains a central unsolved problem in cell biology. As a new investigator, I will use my expertise in biochemistry, cell biology, molecular genetics, and retinal neurobiology to explore the mechanisms involved in delivering signaling and structural proteins to their final destination. My research will focus on investigating the outer segment trafficking of disc and plasma membrane proteins, as well as elucidating how outer segment proteins are segregated between the two functional membrane subdomains – discs and plasma membrane. My proposal has broad implications to understanding the pathobiological processes underlying cases of retinal degenerative diseases and ciliopathy disorders.

项目总结 视觉的第一步发生在视网膜，光被光感受器的外层捕捉到 细胞。这种感光细胞器是一种改良的初级纤毛，具有独特的结构(数百个紧密的 由质膜包裹的堆叠的盘膜)，其包含一组精英信号和 结构蛋白。由于蛋白质是在细胞体中合成的，它们需要离散的细胞内运输 要交付给外部部分的机械装置。这些贩运机制对发展至关重要。 和光感受器的一般维持，因为外节是一个动态的结构，必须 不断更新。了解蛋白质在亚细胞内分布的机制仍然是一个 细胞生物学中尚未解决的核心问题。作为一名新的研究人员，我将利用我在生物化学、细胞 生物学、分子遗传学和视网膜神经生物学，探索与分娩有关的机制 信号和结构蛋白到达他们的最终目的地。我的研究将集中在调查外部 圆盘和质膜蛋白的片段运输，以及阐明外段蛋白是如何 被分离在两个功能膜亚结构域--圆盘和质膜之间。我的 这一建议对理解视网膜病变的病理生物学过程具有广泛的意义。 退行性疾病和睫毛病变。