视紫红质是视杆细胞光信号转导通路中的一个重要蛋白，它不仅对视网膜的功能至关重要，对于视杆细胞外节的形成也起重要的调节作用。视紫红质在视杆细胞的内节合成后，通过胞内蛋白转运机制被运送到外节。视紫红质运输到外节依赖于其C末端的定位序列，视紫红质的C末端序列序列发生突变会导致视网膜色素变性。在体外，动力蛋白Dynein的一条轻链Tctex-1可与紫红质的C末端相互作用，介导视动力蛋白驱动带视紫红质的膜泡沿着微管移动。另外，动力蛋白的另一个轻链LC8也可能参与视紫红质的在感光细胞内的运输。本项目旨在通过构建Tctex-1和LC8的视杆细胞特异的条件敲除小鼠模型，研究Tctex-1和LC8在内体调节视紫红以及其他膜蛋白转运的机制，阐明体内视紫红质的胞内转运机制；并通过生化等其他手段，寻找与视紫红质C末端相互作用的蛋白，进一步深入了解视紫红质胞内转运过程，同时可能发现新的视网膜致病基因。

Rhodopsin is one of components involved in phototransduction in photoreceptors. It is not only important for retinal function, but also plays a key role in regulation of development of photoreceptor outer segments. Rhodopsin is synthesized in photoreceptor inner segments followed by delivery to outer segments through the mechanism of intracellular protein transport. Trafficking rhodopsin to outer segments depends on the targeting signal located at the C-terminus of rhodopsin. Mutation of the C-terminal sequence of rhodopsin leads to retinitis pigmentosa. The in vitro assays indicated that a light chain of dynein, Tctex-1, could interact with the C-terminus of rhodopsin. Tctex-1 containing dynein could mediate movement of rhodopsin-bearing vesicles along microtubule. Additionally, LC8, another light chain of dynein could be also invovled in intracelluar transport of rhodopsin and other membrane proteins. This proposal is aimed to dissect the in vivo role of Tctex-1 and LC8 in regulation of rhodopsin and other membranes proteins by generating rod photoreceptor-specific knockout mice， by which we can elucidate the mechanism of inivo intercellular transport of rhodopsin. Meanwhile, we attempt to search additional proteins which can interact with the C-terminus of rhodopsin by biochemical approaches, further getting inside into intracellular transport process of rhodopsin. Thereby, we may discover new genes for retinal degeneration.