Dr. Thomas Willnow
Max-Delbrück-Centrum für Molekulare Medizin, Berlin-Buch
Functional analysis of the LDL receptor gene family
The low density lipoprotein (LDL) receptor gene family encompasses a class of endocytic receptors that exhibit structural similarities to the LDL receptor. Members of this gene family are present both in vertebrate and non-vertebrate species. The role of the LDL receptor in the metabolism of lipoproteins is very much established. In contrast, little is known about the functional significance of other members of this gene family. In our studies, we have used the gene targeting approach to generate mice lacking individual receptors and to uncover the consequences of the receptor gene defects in vivo. In these studies, we have been able to demonstrate that the LDL receptor-related protein (LRP) is a receptor that mediates the endocytic uptake of dietary lipoproteins, so called chylomicron remnants, into the liver. The existence of such a chylomicron remnant receptor has long been anticipated. Further studies identified the importance of megalin, another member of the LDL receptor gene family, for the embryonic lipoprotein metabolism and the homeostasis of lipophilic vitamins. In addition, gene targeting experiments uncovered the crucial role played by escort proteins or chaperones in biosynthesis and intracellular transport of LDL receptor-related receptors.