Cubilin and megalin: Partners in lipoprotein and vitamin metabolism

Members of the low-density lipoprotein receptor (LDLR) family are unrivalle d for their ability to endocytose and target ligands to lysosomes for degra dation. Their endocytic and catabolic funtions make them essential to homeo static regulation of the level and activity of their ligands in biological fluids and interstitial spaces. Over the last few years it has become evide nt that the endocytic function of members of the LDLR family is employed by other kinds of cell surface receptors. Recently, the low-density lipoprote in receptor related protein-2 (megalin) was shown to act in concert with cu blin, a receptor for high-density lipoproteins (HDL)/apolipoprotein A-I (ap oA-I), intrinsic factor-vitamin B-12 and albumin to mediate ligand endocyto sis. In this article, we review the state of knowledge pertaining to cubuli n and megalin, emphasizing their joint roles in both lipoprotein and vitami n metabolism. (C) 2001, Elsevier Science Inc. All rights reserved.