Cubilin and megalin: partners in lipoprotein and vitamin metabolism

Abstract

Members of the low-density lipoprotein receptor (LDLR) family are unrivalled for their ability to endocytose and target ligands to lysosomes for degradation. Their endocytic and catabolic functions make them essential to homeostatic regulation of the level and activity of their ligands in biological fluids and interstitial spaces. Over the last few years it has become evident that the endocytic function of members of the LDLR family is employed by other kinds of cell surface receptors. Recently, the low-density lipoprotein receptor related protein-2 (megalin) was shown to act in concert with cubilin, a receptor for high-density lipoproteins (HDL)/apolipoprotein A-I (apoA-I), intrinsic factor-vitamin B12 and albumin to mediate ligand endocytosis. In this article, we review the state of knowledge pertaining to cubilin and megalin, emphasizing their joint roles in both lipoprotein and vitamin metabolism.