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

Nature Medicine volume 5, pages 656661 (1999) | Download Citation

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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.

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Acknowledgements

The technical assistance of K. Lassen is acknowledged. The patients are thanked for their cooperation and S. Lindh, for sample collection. U. Gerdes and J. Møller are thanked for the cholesterol and creatinin measurements. J. Gliemann is thanked for comments on the manuscript. The work was financially supported by the Novo Nordisk Foundation, the Danish Medical Research Council, the Danish Biomembrane Center, Aarhus University Research Foundation, the Velux Foundation, a contract from ARC (9914, le Ministére des Affaires Etrangéres, France, NIH grant DK45341 (J.C.F.) and National Cancer Institute grant P30 CA16058.

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Affiliations

  1. Department of Medical Biochemistry, University of Aarhus , Denmark

    • Renata Kozyraki
    • , Mette Kristiansen
    • , Christian Jacobsen
    •  & Søren K. Moestrup
  2. Department of Microbiology, Michigan State University , East Lansing, Michigan, USA

    • John Fyfe
  3. Department of Medicine and Cardiology A, Aarhus University Hospital, Denmark

    • Christian Gerdes
  4. Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark

    • Shiying Cui
    •  & Erik Ilsø Christensen
  5. Division of Human Cancer Genetics, Department of Microbiology and Immunology, Comprehensive Cancer Center, Ohio state University, Columbus, Ohio, USA

    • Maria Aminoff
    • , Albert de la Chapelle
    •  & Ralf Krahe
  6. Folkhälsan Institute of Genetics, University of Helsinki, Finland

    • Maria Aminoff
    • , Albert de la Chapelle
    •  & Ralf Krahe
  7. Institut National de la Santé et de la Recherche Medicale, U489, Hopital Tenon, Paris, France

    • Pierre J. Verroust

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https://doi.org/10.1038/9504