Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Mol Biol Cell. 2011 Apr;22(7):921-30. doi: 10.1091/mbc.E10-09-0792. Epub 2011 Feb 9.
The light-detecting outer segments of vertebrate photoreceptors are cilia. Like other cilia, all materials needed for assembly and maintenance are synthesized in the cell body and transported into the cilium. The highly elaborated nature of the outer segment and its high rate of turnover necessitate unusually high levels of transport into the cilium. In this work, we examine the role of the IFT20 subunit of the intraflagellar transport (IFT) particle in photoreceptor cells. IFT20 was deleted in developing cones by a cone-specific Cre and in mature rods and cones by a tamoxifen-activatable Cre. Loss of IFT20 during cone development leads to opsin accumulation in the inner segment even when the connecting cilium and outer segment are still intact. With time this causes cone cell degeneration. Similarly, deletion of IFT20 in mature rods causes rapid accumulation of rhodopsin in the cell body, where it is concentrated at the Golgi complex. We further show that IFT20, acting both as part of the IFT particle and independent of the particle, binds to rhodopsin and RG-opsin. Since IFT20 dynamically moves between the Golgi complex and the connecting cilium, the current work suggests that rhodopsin and opsins are cargo for IFT transport.
脊椎动物光感受器的光探测外节是纤毛。与其他纤毛一样，组装和维持所需的所有物质都是在细胞体中合成的，并被运输到纤毛中。外节高度特化的性质及其高周转率需要异常高水平的运输到纤毛中。在这项工作中，我们研究了内鞭毛运输（IFT）颗粒的 IFT20 亚基在光感受器细胞中的作用。通过特定于锥体的 Cre 和他莫昔芬激活的 Cre，在发育中的锥体中和成熟的锥体和锥体中删除了 IFT20。在锥体发育过程中丢失 IFT20 会导致即使连接纤毛和外节仍然完整，视蛋白在内节中的积累。随着时间的推移，这会导致锥体细胞退化。同样，在成熟的锥体中删除 IFT20 会导致视紫红质在细胞体中快速积累，在那里它集中在高尔基复合体上。我们进一步表明，IFT20 作为 IFT 颗粒的一部分并独立于颗粒发挥作用，与视紫红质和 RG-视蛋白结合。由于 IFT20 在高尔基复合体和连接纤毛之间动态移动，目前的工作表明视紫红质和视蛋白是 IFT 运输的货物。
