From holoprosencephaly to osteopathology: role of multifunctional endocytic receptors in absorptive epithelia

Ann Med. 2003;35(5):290-9. doi: 10.1080/07853890310006488.


Megalin and cubilin are two multifunctional endocytic receptors expressed in many absorptive epithelia including the yolk sac, the renal proximal tubules, and the intestine. In these tissues, the receptors act in concert to mediate the cellular uptake of a variety of lipoproteins and vitamin/ carrier complexes. Recent studies in animal models and in patients suffering from receptor gene defects have highlighted the crucial role played by the receptors in systemic lipid and vitamin homeostasis, and the severe defects that result from receptor dysfunction. Here, we will review the molecular mechanisms that underlie normal receptor activity and that cause disease in the receptor-deficient organism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Diseases / physiopathology
  • Epithelium / metabolism
  • Epithelium / physiology
  • Gene Expression
  • Holoprosencephaly / genetics
  • Holoprosencephaly / physiopathology
  • Humans
  • Kidney Tubules, Proximal / physiopathology
  • Low Density Lipoprotein Receptor-Related Protein-2 / physiology*
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Protein Binding
  • Receptors, Cell Surface / physiology
  • Vitamin B 12 / metabolism
  • Yolk Sac / physiology


  • Low Density Lipoprotein Receptor-Related Protein-2
  • Receptors, Cell Surface
  • intrinsic factor-cobalamin receptor
  • Vitamin B 12