Steinhoff Julia S, Lass Achim, Schupp Michael
Institute of Pharmacology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.
Front Physiol. 2021 Mar 11;12:659977. doi: 10.3389/fphys.2021.659977. eCollection 2021.
Retinol binding protein 4 (RBP4) is a member of the lipocalin family and the major transport protein of the hydrophobic molecule retinol, also known as vitamin A, in the circulation. Expression of RBP4 is highest in the liver, where most of the body's vitamin A reserves are stored as retinyl esters. For the mobilization of vitamin A from the liver, retinyl esters are hydrolyzed to retinol, which then binds to RBP4 in the hepatocyte. After associating with transthyretin (TTR), the retinol/RBP4/TTR complex is released into the bloodstream and delivers retinol to tissues via binding to specific membrane receptors. So far, two distinct RBP4 receptors have been identified that mediate the uptake of retinol across the cell membrane and, under specific conditions, bi-directional retinol transport. Although most of RBP4's actions depend on its role in retinoid homeostasis, functions independent of retinol transport have been described. In this review, we summarize and discuss the recent findings on the structure, regulation, and functions of RBP4 and lay out the biological relevance of this lipocalin for human diseases.
视黄醇结合蛋白4（RBP4）是脂质运载蛋白家族的成员，是循环中疏水分子视黄醇（也称为维生素A）的主要转运蛋白。RBP4在肝脏中的表达最高，人体大部分维生素A储备以视黄酯的形式储存在肝脏中。为了从肝脏中动员维生素A，视黄酯被水解为视黄醇，然后视黄醇在肝细胞中与RBP4结合。与甲状腺素转运蛋白（TTR）结合后，视黄醇/RBP4/TTR复合物释放到血液中，并通过与特定膜受体结合将视黄醇输送到组织。到目前为止，已鉴定出两种不同的RBP4受体，它们介导视黄醇跨细胞膜的摄取，并在特定条件下介导视黄醇的双向转运。尽管RBP4的大多数作用取决于其在类维生素A稳态中的作用，但也有与视黄醇转运无关的功能被描述。在这篇综述中，我们总结并讨论了关于RBP4的结构、调节和功能的最新发现，并阐述了这种脂质运载蛋白与人类疾病的生物学相关性。
