leupeptins and Vitamin-B-12-Deficiency

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.

Topics: Anemia, Megaloblastic; Animals; Antibodies; Apolipoprotein A-I; Case-Control Studies; Chloroquine; Chromatography, Affinity; Dog Diseases; Dogs; Endocytosis; Epithelial Cells; Female; Humans; Iodine Radioisotopes; Kidney; Leupeptins; Lipoproteins, HDL; Malabsorption Syndromes; Male; Rats; Rats, Wistar; Receptors, Cell Surface; Reference Values; Syndrome; Vitamin B 12 Deficiency; Yolk Sac