The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein

Nat Med. 1999 Jun;5(6):656-61. doi: 10.1038/9504.

Abstract

Cubilin is the intestinal receptor for the endocytosis of intrinsic factor-vitamin B12. However, several lines of evidence, including a high expression in kidney and yolk sac, indicate it may have additional functions. We isolated apolipoprotein A-I (apoA-I), the main protein of high-density lipoprotein (HDL), using cubilin affinity chromatography. Surface plasmon resonance analysis demonstrated a high-affinity binding of apoA-I and HDL to cubilin, and cubilin-expressing yolk sac cells showed efficient 125I-HDL endocytosis that could be inhibited by IgG antibodies against apoA-I and cubilin. The physiological relevance of the cubilin-apoA-I interaction was further emphasized by urinary apoA-I loss in some known cases of functional cubilin deficiency. Therefore, cubilin is a receptor in epithelial apoA-I/HDL metabolism.

Publication types

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

MeSH terms

  • Anemia, Megaloblastic / genetics
  • Anemia, Megaloblastic / metabolism
  • Animals
  • Antibodies / pharmacology
  • Apolipoprotein A-I / genetics*
  • Apolipoprotein A-I / immunology
  • Apolipoprotein A-I / metabolism*
  • Case-Control Studies
  • Chloroquine / pharmacology
  • Chromatography, Affinity
  • Dog Diseases / genetics
  • Dog Diseases / metabolism
  • Dogs
  • Endocytosis / physiology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Iodine Radioisotopes / metabolism
  • Kidney / metabolism
  • Leupeptins / pharmacology
  • Lipoproteins, HDL / metabolism*
  • Malabsorption Syndromes / genetics
  • Malabsorption Syndromes / metabolism
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Reference Values
  • Syndrome
  • Vitamin B 12 Deficiency / genetics
  • Vitamin B 12 Deficiency / metabolism
  • Yolk Sac / cytology
  • Yolk Sac / drug effects
  • Yolk Sac / metabolism

Substances

  • Antibodies
  • Apolipoprotein A-I
  • Iodine Radioisotopes
  • Leupeptins
  • Lipoproteins, HDL
  • Receptors, Cell Surface
  • intrinsic factor-cobalamin receptor
  • Chloroquine
  • leupeptin