The first steps of vision take place in the ciliary outer segment compartment of photoreceptor cells. The protein composition of outer segments is uniquely suited to perform this function. The most abundant among these proteins is the visual pigment, rhodopsin, whose outer segment trafficking involves intraflagellar transport (IFT). Here, we report three major findings from the analysis of mice in which ciliary transport was acutely impaired by conditional knockouts of IFT-B subunits. First, we demonstrate the existence of a sorting mechanism whereby mislocalized rhodopsin is recruited to and concentrated in extracellular vesicles prior to their release, presumably to protect the cell from adverse effects of protein mislocalization. Second, reducing rhodopsin expression significantly delays photoreceptor degeneration caused by IFT disruption, suggesting that controlling rhodopsin levels may be an effective therapy for some cases of retinal degenerative disease. Last, the loss of IFT-B subunits does not recapitulate a phenotype observed in mutants of the BBSome (another ciliary transport protein complex relying on IFT) in which non-ciliary proteins accumulate in the outer segment. Whereas it is widely thought that the role of the BBSome is to primarily participate in ciliary transport, our data suggest that the BBSome has another major function independent of IFT and possibly related to maintaining the diffusion barrier of the ciliary transition zone.

中文翻译：

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鞭毛内运输对感光细胞的区室化和维持的贡献


视觉的第一步发生在感光细胞的睫状外段室中。外节的蛋白质组成非常适合执行此功能。这些蛋白质中最丰富的是视觉色素视紫红质，其外段运输涉及鞭毛内运输（IFT）。在这里，我们报告了对小鼠进行分析的三个主要发现，在这些小鼠中，条件性敲除 IFT-B 亚基会严重损害纤毛运输。首先，我们证明了存在一种分选机制，通过该机制，错误定位的视紫红质在释放之前被募集到细胞外囊泡中并浓缩，大概是为了保护细胞免受蛋白质错误定位的不利影响。其次，减少视紫红质的表达可以显着延缓由 IFT 破坏引起的光感受器变性，这表明控制视紫红质水平可能是治疗某些视网膜变性疾病的有效疗法。最后，IFT-B 亚基的丢失并不能重现在 BBSome（另一种依赖于 IFT 的纤毛转运蛋白复合物）突变体中观察到的表型，其中非纤毛蛋白在外段积聚。尽管人们普遍认为 BBSome 的作用主要是参与纤毛运输，但我们的数据表明 BBSome 具有独立于 IFT 的另一个主要功能，并且可能与维持纤毛过渡区的扩散屏障有关。