Wang Tao, Jiao Yuchen, Montell Craig
Department of Biological Chemistry, Department of Neuroscience, and Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
J Cell Biol. 2007 Apr 23;177(2):305-16. doi: 10.1083/jcb.200610081.
Dietary carotenoids are precursors for the production of retinoids, which participate in many essential processes, including the formation of the photopigment rhodopsin. Despite the importance of conversion of carotenoids to vitamin A (all-trans-retinol), many questions remain concerning the mechanisms that promote this process, including the uptake of carotenoids. We use the Drosophila visual system as a genetic model to study retinoid formation from beta-carotene. In a screen for mutations that affect the biosynthesis of rhodopsin, we identified a class B scavenger receptor, SANTA MARIA. We demonstrate that SANTA MARIA functions upstream of vitamin A formation in neurons and glia, which are outside of the retina. The protein is coexpressed and functionally coupled with the beta, beta-carotene-15, 15'-monooxygenase, NINAB, which converts beta-carotene to all-trans-retinal. Another class B scavenger receptor, NINAD, functions upstream of SANTA MARIA in the uptake of carotenoids, enabling us to propose a pathway involving multiple extraretinal cell types and proteins essential for the formation of rhodopsin.
膳食类胡萝卜素是视黄醇生成的前体物质,视黄醇参与许多重要过程,包括光色素视紫红质的形成。尽管类胡萝卜素转化为维生素A(全反式视黄醇)很重要,但关于促进这一过程的机制,包括类胡萝卜素的摄取,仍有许多问题。我们利用果蝇视觉系统作为遗传模型来研究β-胡萝卜素生成视黄醇的过程。在一项筛选影响视紫红质生物合成的突变的研究中,我们鉴定出一种B类清道夫受体,即圣玛丽亚(SANTA MARIA)。我们证明,圣玛丽亚在视网膜外的神经元和神经胶质细胞中,在维生素A形成的上游发挥作用。该蛋白与β,β-胡萝卜素-15,15'-单加氧酶NINAB共表达且功能耦合,NINAB可将β-胡萝卜素转化为全反式视黄醛。另一种B类清道夫受体NINAD在类胡萝卜素摄取过程中,在圣玛丽亚的上游发挥作用,这使我们能够提出一条涉及多种视网膜外细胞类型和视紫红质形成所必需蛋白质的途径。