Cubilin, the endocytic receptor for intrinsic factor-vitamin B(12) 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 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.
Hammad
S M
SM
Medical University of South Carolina, Department of Cell Biology, Charleston, SC 29425, USA.
Stefansson
S
S
Twal
W O
WO
Drake
C J
CJ
Fleming
P
P
Remaley
A
A
Brewer
H B
HB
Argraves
W S
WS
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000378:metabolism; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000378:metabolism; D002352:Carrier Proteins; D002846:Chromatography, Affinity; D004705:Endocytosis / Q000502:physiology*; D004707:Endoderm / Q000502:physiology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface / Q000502:physiology*; D018110:Receptors, Lipoprotein / Q000302:isolation & purification / Q000378:metabolism*; D015017:Yolk Sac / Q000502:physiology
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D008562:Membrane Glycoproteins; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C031616:high density lipoprotein receptors; C029486:intrinsic factor-cobalamin receptor; C075197:high density lipoprotein binding protein