Aster proteins mediate carotenoid transport in mammalian cells.
Aster proteins mediate carotenoid transport in mammalian cells.
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DOI：
10.1073/pnas.2200068119
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发表时间：
2022-04-12
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
类胡萝卜素色素在脊椎动物组织中以特定的模式积累，并作为着色剂、发色团和激素前体发挥重要作用。然而，促进这些亲脂性色素在细胞内运输的蛋白质尚未被鉴定。我们提供的证据表明，紫菀蛋白是这个过程的关键组成部分，并表明它们以高亲和力结合色素。我们在小鼠中观察到，类胡萝卜素在表达Aster-B的组织中积累，这种积累可以通过BCO 2蛋白的酶促周转来防止。因此，我们发现相反的表达模式的Aster-B蛋白和BCO 2在人类视网膜，似乎有助于独特的类胡萝卜素浓度在黄斑。一些哺乳动物组织独特地集中类胡萝卜素，但这种积累的潜在生化机制尚未完全阐明。例如，灵长类眼睛的中央视网膜显示出高水平的类胡萝卜素、叶黄素和玉米黄质，而啮齿动物视网膜中基本上不存在这些色素。我们以前确定的清道夫受体类B 1型和酶β-胡萝卜素加氧酶-2（BCO 2）的关键组成部分，确定类胡萝卜素的浓度在组织中。我们现在提供的证据表明，紫菀（含GRAM结构域）蛋白，最近认识到他们的作用，在非囊泡胆固醇运输，从事类胡萝卜素代谢。我们的分析表明，StART样的脂质结合结构域的紫菀蛋白可以容纳庞大的色素，并结合它们具有高亲和力。我们进一步表明，类胡萝卜素和胆固醇竞争相同的结合位点。我们建立了一个细菌测试系统，以证明小鼠和人类Aster蛋白的StART样结构域可以从生物膜中提取类胡萝卜素。缺乏类胡萝卜素分解代谢酶BCO 2的小鼠将类胡萝卜素集中在表达Aster-B蛋白的组织中，如肾上腺。值得注意的是，Aster-B在人类视网膜中表达，但在小鼠视网膜中不表达。在视网膜内，Aster-B和BCO 2在中央与周边部分表现出相反的表达模式。总之，我们的研究揭示了细胞内类胡萝卜素转运的生化基础，并暗示Aster-B参与了人类视网膜黄斑色素浓度的途径。
Carotenoid pigments accumulate in specific patterns in vertebrate tissues and play important roles as colorants, chromophores, and hormone precursors. However, proteins that facilitate transportation of these lipophilic pigments within cells have not been identified. We provide evidence that Aster proteins are key components for this process and show that they bind the pigments with high affinity. We observed in mice that carotenoids accumulate in tissues that express Aster-B and this accumulation can be prevented by enzymatic turnover by the BCO2 protein. Accordingly, we found opposing expression patterns of the Aster-B protein and BCO2 in the human retina that seemingly contribute to the unique carotenoid concentration in the macula lutea. Some mammalian tissues uniquely concentrate carotenoids, but the underlying biochemical mechanism for this accumulation has not been fully elucidated. For instance, the central retina of the primate eyes displays high levels of the carotenoids, lutein, and zeaxanthin, whereas the pigments are largely absent in rodent retinas. We previously identified the scavenger receptor class B type 1 and the enzyme β-carotene-oxygenase-2 (BCO2) as key components that determine carotenoid concentration in tissues. We now provide evidence that Aster (GRAM-domain-containing) proteins, recently recognized for their role in nonvesicular cholesterol transport, engage in carotenoid metabolism. Our analyses revealed that the StART-like lipid binding domain of Aster proteins can accommodate the bulky pigments and bind them with high affinity. We further showed that carotenoids and cholesterol compete for the same binding site. We established a bacterial test system to demonstrate that the StART-like domains of mouse and human Aster proteins can extract carotenoids from biological membranes. Mice deficient for the carotenoid catabolizing enzyme BCO2 concentrated carotenoids in Aster-B protein-expressing tissues such as the adrenal glands. Remarkably, Aster-B was expressed in the human but not in the mouse retina. Within the retina, Aster-B and BCO2 showed opposite expression patterns in central versus peripheral parts. Together, our study unravels the biochemical basis for intracellular carotenoid transport and implicates Aster-B in the pathway for macula pigment concentration in the human retina.
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影响因子：
4.5
作者：
Eriksson, Jonas;Larson, Greger;Gunnarsson, Ulrika;Bed'hom, Bertrand;Tixier-Boichard, Michele;Stromstedt, Lina;Wright, Dominic;Jungerius, Annemieke;Vereijken, Addie;Randi, Ettore;Jensen, Per;Andersson, Leif
通讯作者：
Andersson, Leif
影响因子：
4
作者：
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通讯作者：
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影响因子：
3.4
作者：
Imanishi, Y;Li, G;Palczewski, K
通讯作者：
Palczewski, K
影响因子：
3.4
作者：
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通讯作者：
Berendschot, Tos T. J. M.
影响因子：
4.8
作者：
Bhosale, P;Larson, AJ;Bernstein, PS
通讯作者：
Bernstein, PS