Megalin- and cubilin-mediated endocytosis of protein-bound vitamins, lipids, and hormones in polarized epithelia

• Published in: Annual review of nutrition Vol. 21; pp. 407 - 428
• Main Authors: MOESTRUP, Søren K, VERROUST, Pierre J
• Format: Journal Article
• Language: English
• Published: Palo Alto, CA Annual Reviews 01.01.2001; Annual Reviews, Inc
• Subjects: Animals; Binding Sites; Biological and medical sciences; Cell physiology; Cell Polarity; Endocytosis; Epithelium - physiology; Epithelium - ultrastructure; Fundamental and applied biological sciences. Psychology; Hormones; Hormones - metabolism; Humans; Kidney - physiology; Ligands; Lipid Metabolism; Lipids; Low Density Lipoprotein Receptor-Related Protein-2 - analysis; Low Density Lipoprotein Receptor-Related Protein-2 - chemistry; Low Density Lipoprotein Receptor-Related Protein-2 - physiology; Molecular and cellular biology; Proteins - metabolism; Receptors, Cell Surface - analysis; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - physiology; Thyroid Gland - physiology; Vitamins; Vitamins - metabolism; Yolk Sac - physiology; Hormone; Endocytosis; Vitamin D; Vitamin; Epithelial cell; Lipids; Polarity; B-Vitamins; Review; Cyanocobalamin; Retinol
• ISSN: 0199-9885; 1545-4312
• DOI: 10.1146/annurev.nutr.21.1.407

Polarized epithelia have several functional and morphological similarities, including a high capacity for uptake of various substances present in the fluids facing the apical epithelial surfaces. Studies during the past decade have shown that receptor-mediated endocytosis, rather than nonspecific pinocytosis, accounts for the apical epithelial uptake of many carrier-bound nutrients and hormones. The two interacting receptors of distinct evolutionary origin, megalin and cubilin, are main receptors in this process. Both receptors are apically expressed in polarized epithelia, in which they function as biological affinity matrices for overlapping repertoires of ligands. The ability to bind multiple ligands is accounted for by a high number of replicated low-density lipoprotein receptor type-A repeats in megalin and CUB (complement C1r/C1s, Uegf, and bone morphogenic protein-1) domains in cubilin. Here we summarize and discuss the structural, genetic, and functional aspects of megalin and cubilin, with emphasis on their function as receptors for uptake of protein-associated vitamins, lipids, and hormones.