Essential role of nephrocystin in photoreceptor intraflagellar transport in mouse
Essential role of nephrocystin in photoreceptor intraflagellar transport in mouse
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DOI：
10.1093/hmg/ddp068
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发表时间：
2009-05-01
影响因子：
3.5
通讯作者：
Li, Hung
中科院分区：
文献类型：
--
作者：
Jiang, Si-Tse;Chiou, Yuan-Yow;Li, Hung
肾囊藻毒素突变是导致儿童肾功能衰竭最常见的遗传性原因，是青少年肾炎的主要原因。Nephrocystin定位于上皮细胞的纤毛移行区或其类似结构，连接视网膜光感受器的纤毛。因此，与肾炎相关的视网膜变性可以用功能性睫毛缺陷来解释。然而，肾囊藻毒素在普通上皮细胞和光感受器纤毛组装和维持中的作用尚不清楚。在这里，我们利用Nphp1靶向突变小鼠和表达EmGFP标记的肾囊藻毒素的转基因小鼠来证明位于纤毛轴丝连接处的肾囊藻毒素可以影响光感受器内外节间交通机械的分选机制和运输效率。这种交通机械现在被认为是鞭毛内运输(IFT)；一种基于微管的运输系统，由发动机、IFT颗粒和相关的货物分子组成。Nephrocystin似乎控制着一些IFT颗粒成分沿连接纤毛的移动，从而调节这种节间交通。我们的新发现为解开肾囊藻毒素在IFT机制中的调控机制提供了线索。
Nephrocystin mutations account for the vast majority of juvenile nephronophthisis, the most common inherited cause of renal failure in children. Nephrocystin has been localized to the ciliary transition zone of epithelial cells or its analogous structure, connecting cilium of retinal photoreceptors. Thus, the retinal degeneration associated with nephronophthisis may be explained by a functional ciliary defect. However, the function of nephrocystin in cilium assembly and maintenance of common epithelial cells and photoreceptors is still obscure. Here, we used Nphp1-targeted mutant mice and transgenic mice expressing EmGFP-tagged nephrocystin to demonstrate that nephrocystin located at connecting cilium axoneme can affect the sorting mechanism and transportation efficiency of the traffic machinery between inner and outer segments of photoreceptors. This traffic machinery is now recognized as intraflagellar transport (IFT); a microtubule-based transport system consisting of motors, IFT particles and associated cargo molecules. Nephrocystin seems to control some of the IFT particle components moving along the connecting cilia so as to regulate this inter-segmental traffic. Our novel findings provide a clue to unraveling the regulatory mechanism of nephrocystin in IFT machinery.