Cubilin, the endocytic receptor for intrinsic factor-vitamin B12 complex, mediates high-density lipoprotein holoparticle endocytosis

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 intrin...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 96; no. 18; pp. 10158 - 10163
Main Authors Hammad, S.M, Stefansson, S, Twal, W.O, Drake, C.J, Fleming, P, Remaley, A, Brewer, H.B. Jr, Argraves, W.S
Format Journal Article
LanguageEnglish
Published National Acad Sciences 31.08.1999
The National Academy of Sciences
Subjects
apolipoproteins
binding proteins
Biological Sciences
carcinoma
cell lines
endocytosis
f9 cells
high density lipoprotein
humans
mice
protein degradation
receptors
teratocarcinoma cells
uptake
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Summary: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.
Bibliography:To whom reprint requests should be addressed.
Communicated by Marilyn Gist Farquhar, University of California at San Diego, La Jolla, CA
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.18.10158