Understanding Photoreceptor Trafficking Pathways to the Outer Segment

项目摘要 视觉的第一步发生在视网膜上，光被感光器的外节捕获 细胞这种感光细胞器是一种经过修饰的初级纤毛，具有独特的结构（数百个紧密排列在一起）。 由质膜包围的堆叠的盘膜），其包含一组精英信号传导， 结构蛋白由于蛋白质是在细胞索马中合成的，它们需要离散的细胞内运输 要传递到外部段的机制。这些贩运机制对发展至关重要 和感光细胞的一般维护，因为外节是一个动态结构，必须 不断更新。了解蛋白质亚细胞分布的机制仍然是一个挑战。 细胞生物学的核心未解决问题。作为一名新的调查员，我将运用我在生物化学，细胞， 生物学、分子遗传学和视网膜神经生物学，以探索参与递送的机制。 信号传导和结构蛋白到达最终目的地。我的研究将集中于调查 节运输的光盘和质膜蛋白，以及阐明如何外节蛋白 在两个功能性膜亚结构域-盘和质膜之间分离。我 该提案对理解视网膜病变的病理生物学过程具有广泛的意义。 退行性疾病和纤毛病病症。

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.