Kozyraki R, Fyfe J, Kristiansen M, Gerdes C, Jacobsen C, Cui S, Christensen E I, Aminoff M, de la Chapelle A, Krahe R, Verroust P J, Moestrup S K
Department of Medical Biochemistry, University of Aarhus, Denmark.
Nat Med. 1999 Jun;5(6):656-61. doi: 10.1038/9504.
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.
Cubilin是内因子-维生素B12内吞作用的肠道受体。然而,包括在肾脏和卵黄囊中高表达在内的多条证据表明,它可能具有其他功能。我们使用cubilin亲和层析法分离了高密度脂蛋白(HDL)的主要蛋白质载脂蛋白A-I(apoA-I)。表面等离子体共振分析表明apoA-I和HDL与cubilin具有高亲和力结合,并且表达cubilin的卵黄囊细胞显示出有效的125I-HDL内吞作用,该作用可被抗apoA-I和cubilin的IgG抗体抑制。在一些已知的功能性cubilin缺乏病例中,尿apoA-I丢失进一步强调了cubilin-apoA-I相互作用的生理相关性。因此,cubilin是上皮细胞apoA-I/HDL代谢中的一种受体。