Nimpf J, Schneider W J
Institute of Medical Biochemistry, Department of Molecular Genetics, University and Biocenter Vienna, Dr. Bohr Gasse 9/2, A-1030, Vienna, Austria.
Biochim Biophys Acta. 2000 Dec 15;1529(1-3):287-98. doi: 10.1016/s1388-1981(00)00155-4.
The discovery of an ever growing number of low density lipoprotein (LDL) receptor gene family members has triggered research into many different directions. Here we first summarize the results of classical studies on the role of the LDL receptor in cholesterol transport, the structure/function relationships delineated with the help of LDL receptor mutations in familial hypercholesterolemia, and the elegant way in which cells regulate cholesterol at the transcriptional level. The second part deals with a multifunctional, structurally very close relative, the very low density lipoprotein (VLDL) receptor. While it is involved in lipoprotein transport in certain tissues and species, detailed studies on its function have generated new knowledge about the growing spectrum of ligands and about exciting and unexpected aspects of receptor biology. In particular, these investigations have elucidated the roles of LDL receptor gene family members in ligand-mediated signal transduction. In the third part of this review article, we provide first insight into the roles of the VLDL receptor and of another small relative, the so-called apolipoprotein E receptor-2, in such signaling processes. These findings suggest that to date, only the tip of an iceberg has been uncovered.
越来越多低密度脂蛋白（LDL）受体基因家族成员的发现引发了多方向的研究。在此，我们首先总结关于LDL受体在胆固醇转运中的作用的经典研究结果、借助家族性高胆固醇血症中的LDL受体突变所描绘的结构/功能关系，以及细胞在转录水平调节胆固醇的精妙方式。第二部分探讨一种多功能且结构上非常相近的亲属——极低密度脂蛋白（VLDL）受体。虽然它在某些组织和物种中参与脂蛋白转运，但对其功能的详细研究产生了关于不断增加的配体谱以及受体生物学中令人兴奋和意想不到方面的新知识。特别是，这些研究阐明了LDL受体基因家族成员在配体介导的信号转导中的作用。在这篇综述文章的第三部分，我们首次深入了解VLDL受体和另一个小亲属——所谓的载脂蛋白E受体-2在这类信号转导过程中的作用。这些发现表明，迄今为止，我们只揭开了冰山一角。
