From cholesterol transport to signal transduction: low density lipoprotein receptor, very low density lipoprotein receptor, and apolipoprotein E receptor-2

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.