SR-BI Undergoes Cholesterol-stimulated Transcytosis to the Bile Canaliculus in Polarized WIF-B Cells

The scavenger receptor BI (SR-BI) is highly expressed in hepatocytes, where it mediates the uptake of lipoprotein cholesterol, promotes the secretion of cholesterol into bile, and protects against atherosclerosis. Despite a strong correlation between the hepatic expression of SR-BI and biliary chole...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-01, Vol.282 (2), p.1445-1455
Main Authors: Harder, Christopher J., Meng, Andrew, Rippstein, Peter, McBride, Heidi M., McPherson, Ruth
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis - metabolism
Bacterial Proteins - genetics
Bile Canaliculi - cytology
Bile Canaliculi - metabolism
Cell Polarity - physiology
Cells, Cultured
Chlorocebus aethiops
Cholesterol - metabolism
Cholesterol - pharmacology
COS Cells
Humans
Luminescent Proteins - genetics
Microscopy, Fluorescence
Protein Transport - drug effects
Protein Transport - physiology
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Scavenger Receptors, Class B - genetics
Scavenger Receptors, Class B - metabolism
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Summary:The scavenger receptor BI (SR-BI) is highly expressed in hepatocytes, where it mediates the uptake of lipoprotein cholesterol, promotes the secretion of cholesterol into bile, and protects against atherosclerosis. Despite a strong correlation between the hepatic expression of SR-BI and biliary cholesterol secretion, little is known about SR-BI trafficking in response to changes in sterol availability. Using a well characterized polarized hepatocyte cell model, WIF-B, we determine that in cholesterol-depleted cells, SR-BI is extensively located on the basolateral surface, where it can access circulating lipoproteins. However, in response to cholesterol loading, SR-BI undergoes a slow transcytosis to the apical bile canaliculus independently of lipoprotein binding and new protein synthesis. In cholesterol-replete WIF-B cells, SR-BI that resides on the canalicular membrane is dynamically associated with defined microdomains and does not rapidly recycle to and from the subapical or basolateral regions. Taken together, these data demonstrate that hepatic SR-BI transcytosis is regulated by cholesterol and suggest that SR-BI has a stationary function on the bile canaliculus.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M604627200