Cubilin, the endocytic receptor for intrinsic factor-vitamin B 12 complex, mediates high-density lipoprotein holoparticle endocytosis

• DOI: 10.1073/pnas.96.18.10158
• Publication Date: 2002-07-26T14:38:21Z
• Authors: Samar M. Hammad; Steingrimur Stefa...; Waleed O. Twal; Christopher J. Drake; Paul Fleming; Alan Remaley; H. Bryan Brewer; W. Scott Argraves
• Keywords: 0301 basic medicine; Apolipoprotein C-III; Membrane Glycoproteins; Microscopy, Confocal; Apolipoprotein A-I; Endoderm; RNA-Binding Proteins; Receptors, Cell Surface; Chromatography, Affinity; Endocytosis; Kidney Tubules, Proximal; Kinetics; Mice; 03 medical and health sciences; Animals; Humans; Apolipoproteins C; Carrier Proteins; Lipoproteins, HDL; Apolipoprotein A-II; Receptors, Lipoprotein; Yolk Sac

Receptors that endocytose high-density lipoproteins (HDL) have been elusive. Here yolk-sac endoderm-like cells were used to identify an endocytic receptor for HDL. The was isolated by HDL affinity chromatography and identified as cubilin, the recently described intrinsic factor-vitamin B 12 . Cubilin antibodies inhibit endocytosis in mouse embryo endoderm, a prominent site of cubilin expression. Cubilin-mediated is inhibitable 2 , 3 apolipoprotein (apo)A-I, apoA-II, apoE, RAP, but not low-density lipoprotein (LDL), oxidized LDL, VLDL, apoC-I, apoC-III, or heparin. These findings, coupled with fact expressed kidney proximal tubules, suggest role this embryonic acquisition maternal renal catabolism filterable forms