Cellular mechanism of targeting peripherin to the sensory cilium

描述（由申请人提供）：视觉起始于视网膜，其中光被感光细胞的外节细胞器捕获。外节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，外节缺乏用于合成蛋白质的机制，因此依赖于细胞索马中合成的蛋白质的输入。关于蛋白质从其合成位点到外节的细胞内运输知之甚少。只有视色素视紫红质的运输途径已被描述，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标是确定另一个外节蛋白，外周蛋白，是如何交付到外节。选择外周蛋白是因为其外段靶向依赖于与视紫红质不同的基序，表明其可能利用不同的转运机制。我的第二个目标是探索蛋白质靶向图案之间的光感受器和其他类型的睫状细胞的普遍性。我将研究不同类型的纤毛是否使用相同的靶向信息和分子机制来传递蛋白质。该项目对于理解负责将特定蛋白质递送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具有广泛的意义。

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.