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.
R Kozyraki  1 ,  J Fyfe ,  M Kristiansen ,  C Gerdes ,  C Jacobsen ,  S Cui ,  E I Christensen ,  M Aminoff ,  A de la Chapelle ,  R Krahe ,  P J Verroust ,  S K Moestrup
Affiliations
  • 1. Department of Medical Biochemistry, University of Aarhus, Denmark.
PMID: 10371504 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.