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J. Biol. Chem., Vol. 276, Issue 27, 25287-25293, July 6, 2001
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From the High density lipoprotein (HDL) mediates reverse
transport of cholesterol from atheroma foam cells to the liver, but the
mechanisms of hepatic uptake and trafficking of HDL particles are
poorly understood. In contrast to its accepted role as a cell surface receptor, scavenger receptor class B type 1 (SR-BI) is shown to be an
endocytic receptor that mediates HDL particle uptake and recycling, but
not degradation, in both transfected Chinese hamster ovary cells and
hepatocytes. Confocal microscopy of polarized primary
hepatocytes shows that HDL particles enter both the endocytic recycling
compartment and the apical canalicular region paralleling the movement
of SR-BI. In polarized epithelial cells (Madin-Darby canine kidney)
expressing SR-BI, HDL protein and cholesterol undergo selective sorting
with recycling of HDL protein from the basolateral membrane and
secretion of HDL-derived cholesterol through the apical membrane. Thus,
HDL particles, internalized via SR-BI, undergo a novel process of
selective transcytosis, leading to polarized cholesterol transport. A
distinct process not mediated by SR-BI is involved in uptake and
degradation of apoE-free HDL in hepatocytes.
High Density Lipoprotein (HDL) Particle Uptake Mediated by
Scavenger Receptor Class B Type 1 Results in Selective Sorting of HDL
Cholesterol from Protein and Polarized Cholesterol
Secretion*
§,,
Department of Medicine, Division of
Molecular Medicine, Columbia University, New York, New York 10032 and
the ¶ Department of Molecular Genetics and Biochemistry,
University of Pittsburgh, Pittsburgh, Pennsylvania 15219
*
This work was supported by National Institutes of Health
Grant HL22682 (to A. R. T.) and National Institutes of Health
Research Fellowship Award HL09928 (to D. L. S.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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