Multiligand Endocytosis and Congenital Defects: Roles of Cubilin, Megalin and Amnionless

Cubilin and megalin are multiligand receptors that mediate uptake of extracellular ligands. Their function has extensively been studied in the kidney where they play a key role in vitamin B12 and vitamin D homeostasis. Amnionless is a plasma membrane protein that binds to cubilin in various epithelia; the interaction cubilin-amnionless in the gut is crucial for dietary vitamin B12 uptake. Studies in patients with gene defects in these receptors, and animal models with inactivated cubilin, megalin or amnionless suggest an important role in embryonic development and normal growth. In this review we will summarize recent data on the biological function of these receptors and focus on their implication in embryonic nutrition and central nervous system malformations.