Cellular mechanism of targeting peripherin to the sensory cilium

描述（由申请人提供）：视觉开始于视网膜，光在感光细胞的外节细胞器中被捕获。外段的独特之处在于它是一个修饰的初级纤毛，含有大量参与视觉信号转导的蛋白质。值得注意的是，外段缺乏用于合成蛋白质的机制，因此依赖于在细胞体细胞中合成的蛋白质的进口。关于蛋白质从合成位点到外段的细胞内运输，我们所知甚少。目前只描述了视色素视紫红质的运输途径，目前尚不清楚其他蛋白质是否使用相同或不同的途径。因此，我的建议的第一个目的是确定另一种外节蛋白，外周蛋白，是如何传递到外节的。选择外周蛋白是因为它的外段靶向依赖于与视紫红质不同的基序，这表明它可能利用不同的运输机制。我的第二个目标是探索光感受器和其他类型纤毛细胞之间蛋白质靶向基序的普遍性。我将研究不同类型的纤毛是否具有相同的靶向信息和传递蛋白质的分子机制。该项目具有广泛的意义，可以理解负责特定蛋白质传递到外段和其他纤毛的细胞机制，以及阐明运输机制的突变如何导致光感受器的视网膜变性和其他细胞类型的纤毛功能障碍。

DESCRIPTION (provided by applicant): Vision is initiated in the retina where light is captured in the outer segment organelle of photoreceptor cells. The outer segment is unique in that it is a modified primary cilium that contains large quantities of proteins involved in visual signal transduction. Notably, the outer segment lacks the machinery used to synthesize proteins and therefore relies on the import of proteins synthesized in the cell's soma. Very little is known about the intracellular trafficking of proteins from their site of synthesis to the outer segment. Only the trafficking pathway for the visual pigment, rhodopsin, has been described and it is currently unknown whether other proteins use the same or different pathways. Thus the first aim of my proposal is to determine how another outer segment protein, peripherin, is delivered to the outer segment. Peripherin was selected because its outer segment targeting relies on a motif distinct from that of rhodopsin, suggesting that it may utilize a distinct transport mechanism. My second aim is to explore the universality of protein targeting motifs between photoreceptors and other types of ciliary cells. I will examine whether different types of cilia us the same targeting information and molecular machinery to deliver proteins. This project has broad implications for understanding cellular mechanisms responsible for specific protein delivery to the outer segment and other cilia, as well as elucidating how mutations of the trafficking machinery can lead to retinal degeneration in photoreceptors and ciliary dysfunction in other cell types.