Departments of Biological Chemistry and Neuroscience, Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Neurosci. 2012 Mar 7;32(10):3485-91. doi: 10.1523/JNEUROSCI.5350-11.2012.
In mammalian rods and cones, light activation of the visual pigments leads to release of the chromophore, which is then recycled through a multistep enzymatic pathway, referred to as the visual or retinoid cycle. In invertebrates such as Drosophila, a visual cycle was thought not to exist since the rhodopsins are bistable photopigments, which consist of a chromophore that normally stays bound to the opsin following light activation. Nevertheless, we recently described a visual cycle in Drosophila that serves to recycle the free chromophore that is released following light-induced internalization of rhodopsin, and a retinol dehydrogenase (RDH) that catalyzes the first step of the pathway. Here, we describe the identification of a putative RDH, referred to as RDHB (retinol dehydrogenase B), which functions in the visual cycle and in de novo synthesis of the chromophore. RDHB was expressed in the retinal pigment cells (RPCs), where it promoted the final enzymatic reaction necessary for the production of the chromophore. Mutation of rdhB caused moderate light-dependent degeneration of the phototransducing compartment of the photoreceptor cells-the rhabdomeres, reminiscent of the effects of mutations in some human RDH genes. Since the first and last steps in the visual cycle take place in the RPCs, it appears that these cells are the sites of action for this entire enzymatic pathway in Drosophila.
在哺乳动物的视杆和视锥细胞中,视觉色素的光激活导致发色团的释放,然后通过多步酶促途径(称为视觉或类视黄醇循环)进行回收。在像果蝇这样的无脊椎动物中,由于视蛋白是双稳态的光致变色色素,其组成部分是一种发色团,通常在光激活后与视蛋白结合,因此人们认为不存在视觉循环。然而,我们最近在果蝇中描述了一个视觉循环,它用于回收光诱导的视蛋白内化后释放的游离发色团,以及一种催化该途径第一步的视黄醇脱氢酶(RDH)。在这里,我们描述了一种假定的 RDH 的鉴定,称为 RDHB(视黄醇脱氢酶 B),它在视觉循环和发色团的从头合成中起作用。RDHB 在视网膜色素细胞(RPCs)中表达,在那里它促进了生产发色团所需的最后一步酶促反应。rdhb 的突变导致光感受器细胞的光转导隔室 - 纤毛的中度光依赖性退化,这类似于一些人类 RDH 基因突变的影响。由于视觉循环的第一步和最后一步都发生在 RPCs 中,因此这些细胞似乎是果蝇中整个酶促途径的作用部位。