Subfunctionalization of a retinoid-binding protein provides evidence for two parallel visual cycles in the cone-dominant zebrafish retina
Subfunctionalization of a retinoid-binding protein provides evidence for two parallel visual cycles in the cone-dominant zebrafish retina
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DOI：
10.1523/jneurosci.2367-08.2008
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发表时间：
2008-08-13
影响因子：
5.3
通讯作者：
Neuhauss, Stephan C. F.
中科院分区：
文献类型：
--
作者：
Fleisch, Valerie C.;Schonthaler, Helia B.;Neuhauss, Stephan C. F.
在脊椎动物中，光子的吸收导致视锥和视杆视色素的亚视黄基发色团的11-顺式到全反式异构化。为了维持视力，代谢途径（视觉周期）已经进化，将全反式-视网膜再循环回11-顺式-视网膜。典型的视觉周期发生在感光细胞和相邻的视网膜色素上皮细胞（RPE）中。生化分析提供的证据表明，存在一个额外的锥特定的视觉周期，涉及穆勒神经胶质细胞，但其分子成分尚未确定。在这里，我们利用斑马鱼视网膜的研究细胞的视网膜色素脱结合蛋白CRALBP在这一过程中的作用。我们发现斑马鱼基因组编码两个cralbp旁系同源物：cralbp a和cralbp B。这些旁系同源物在视网膜中差异表达。Cralbp a仅在RPE中表达，而Cralbp B定位于Muller细胞。我们使用反义吗啉代方法来敲除每个cralbp基因。11-顺式-视网膜水平的分析表明，视觉发色团再生减少在这两种条件下。视觉性能，视网膜电图评估，显示降低的光敏感性在Cralbp a-和Cralbp b-缺陷的幼虫，但它是更明显的Cralbp b-缺陷的幼虫。Cralbp b缺陷的幼虫也表现出显着的缺陷，在他们的视觉行为。总之，这些数据表明，Cralbp在穆勒细胞中的表达是必不可少的锥视觉，从而提供证据表明，无论是典型的和替代的视觉周期依赖于相同类型的类维生素A结合蛋白。
In vertebrates, the absorption of a photon results in an 11-cis to all-trans isomerization of the retinylidene chromophore of cone and rod visual pigments. To sustain vision, metabolic pathways ( visual cycles) have evolved that recycle all-trans-retinal back to 11-cis-retinal. The canonical visual cycle takes place in photoreceptor cells and the adjacent retinal pigment epithelium (RPE). Biochemical analyses provided evidence for the existence of an additional cone-specific visual cycle involving Muller glia cells, but none of its molecular components has yet been identified. Here we took advantage of the zebrafish retina to investigate the role of the cellular retinaldehyde-binding protein CRALBP in this process. We found that the zebrafish genome encodes two cralbp paralogs: cralbp a and cralbp b. These paralogs are differentially expressed in the retina. Cralbp a is exclusively expressed in the RPE, and Cralbp b is localized to Muller cells. We used an antisense morpholino approach to knock down each cralbp paralog. Analysis of 11-cis-retinal levels revealed that visual chromophore regeneration is diminished under both conditions. Visual performance, as assessed by electroretinography, revealed reduced light sensitivity in both Cralbp a- and Cralbp b-deficient larvae, but it was more pronounced in Cralbp b-deficient larvae. Cralbp b-deficient larvae also exhibited significant deficits in their visual behavior. Together, these data demonstrate that Cralbp expression in Muller cells is essential for cone vision, thereby providing evidence that both the canonical and the alternative visual cycle depend on the same type of retinoid-binding protein.