The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein.
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.
Kozyraki
R
R
Department of Medical Biochemistry, University of Aarhus, Denmark.
Fyfe
J
J
Kristiansen
M
M
Gerdes
C
C
Jacobsen
C
C
Cui
S
S
Christensen
E I
EI
Aminoff
M
M
de la Chapelle
A
A
Krahe
R
R
Verroust
P J
PJ
Moestrup
S K
SK
D000749:Anemia, Megaloblastic / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D002738:Chloroquine / Q000494:pharmacology; D002846:Chromatography, Affinity; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D004705:Endocytosis / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008286:Malabsorption Syndromes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012016:Reference Values; D013577:Syndrome; D014806:Vitamin B 12 Deficiency / Q000235:genetics / Q000378:metabolism; D015017:Yolk Sac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000906:Antibodies; D016632:Apolipoprotein A-I; D007457:Iodine Radioisotopes; D007976:Leupeptins; D008075:Lipoproteins, HDL; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor; D002738:Chloroquine; C032854:leupeptin