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 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.
Harder
Christopher J
CJ
Lipoprotein and Atherosclerosis Group, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada.
Meng
Andrew
A
Rippstein
Peter
P
McBride
Heidi M
HM
McPherson
Ruth
R
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D001648:Bile Canaliculi / Q000166:cytology* / Q000378:metabolism*; D019556:COS Cells; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D008856:Microscopy, Fluorescence; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D008164:Luminescent Proteins; D011994:Recombinant Proteins; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C054562:yellow fluorescent protein, Bacteria; D002784:Cholesterol