Department of Biology, Indiana University, 1001 East Third St, Bloomington, IN 47405, USA.
Dev Biol. 2012 Nov 15;371(2):312-20. doi: 10.1016/j.ydbio.2012.08.024. Epub 2012 Sep 1.
The two fundamental types of photoreceptor cells have evolved unique structures to expand the apical membrane to accommodate the phototransduction machinery, exemplified by the cilia-based outer segment of the vertebrate photoreceptor cell and the microvilli-based rhabdomere of the invertebrate photoreceptor. The morphogenesis of these compartments is integral for photoreceptor cell integrity and function. However, little is known about the elementary cellular and molecular mechanisms required to generate these compartments. Here we investigate whether a conserved cellular mechanism exists to create the phototransduction compartments by examining the functional role of a photoreceptor protein common to both rhabdomeric and ciliated photoreceptor cells, Prominin. First and foremost we demonstrate that the physiological role of Prominin is conserved between rhabdomeric and ciliated photoreceptor cells. Human Prominin1 is not only capable of rescuing the corresponding rhabdomeric Drosophila prominin mutation but also demonstrates a conserved genetic interaction with a second photoreceptor protein Eyes Shut. Furthermore, we demonstrate the Prominin homologs in vertebrate and invertebrate photoreceptors require the same structural features and post-translational modifications for function. Moreover, expression of mutant human Prominin1, associated with autosomal dominant retinal degeneration, in rhabdomeric photoreceptor cells disrupts morphogenesis in ways paralleling retinal degeneration seen in ciliated photoreceptors. Taken together, our results suggest the existence of an ancestral Prominin-directed cellular mechanism to create and model the apical membranes of the two fundamental types of photoreceptor cells into their respective phototransduction compartments.
两种基本类型的光感受器细胞已经进化出独特的结构，以扩大顶膜以容纳光转导机制，以脊椎动物光感受器细胞的基于纤毛的外节和无脊椎动物光感受器的基于微绒毛的光感受器为代表。这些隔室的形态发生对于光感受器细胞的完整性和功能至关重要。然而，对于产生这些隔室所需的基本细胞和分子机制知之甚少。在这里，我们通过研究普遍存在于纤毛状和纤毛状光感受器细胞中的光感受器蛋白 Prominin，来研究是否存在一种保守的细胞机制来创建光转导隔室。首先，我们证明了 Prominin 的生理作用在纤毛状和纤毛状光感受器细胞之间是保守的。人 Prominin1 不仅能够挽救相应的纤毛状果蝇 prominin 突变，而且还与第二个光感受器蛋白 Eyes Shut 表现出保守的遗传相互作用。此外，我们证明了脊椎动物和无脊椎动物光感受器中的 Prominin 同源物需要相同的结构特征和翻译后修饰才能发挥功能。此外，在纤毛状光感受器细胞中表达与常染色体显性视网膜变性相关的突变型人 Prominin1 会以类似于在纤毛状光感受器中看到的视网膜变性的方式破坏形态发生。总之，我们的研究结果表明存在一种古老的 Prominin 导向的细胞机制，可以将两种基本类型的光感受器细胞的顶膜分别构建成各自的光转导隔室。
