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PMID: 10468579 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Hammad SM, Stefansson S, Twal WO, Drake CJ, Fleming P, Remaley A, Brewer HB, Argraves WS

Abstract

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

MeSH Terms
Animals Apolipoprotein A-I/metabolism Apolipoprotein A-II/metabolism Apolipoprotein C-III Apolipoproteins C/metabolism Carrier Proteins Chromatography, Affinity Endocytosis/physiology Endoderm/physiology Humans Kidney Tubules, Proximal/physiology Kinetics Lipoproteins, HDL/metabolism Membrane Glycoproteins/physiology Mice Microscopy, Confocal RNA-Binding Proteins Receptors, Cell Surface/physiology Receptors, Lipoprotein/isolation & purification,metabolism Yolk Sac/physiology
Chemicals
Apolipoprotein A-I Apolipoprotein A-II Apolipoprotein C-III Apolipoproteins C Carrier Proteins Lipoproteins, HDL Membrane Glycoproteins RNA-Binding Proteins Receptors, Cell Surface Receptors, Lipoprotein high density lipoprotein receptors intrinsic factor-cobalamin receptor high density lipoprotein binding protein
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Hammad S M
Medical University of South Carolina, Department of Cell Biology, Charleston, SC 29425, USA.
Stefansson S
Twal W O
Drake C J
Fleming P
Remaley A
Brewer H B
Argraves W S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1999-08-31
Pages
10158-63
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC17859
Subset
IM
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