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Originally published In Press as doi:10.1074/jbc.M604627200 on November 14, 2006

J. Biol. Chem., Vol. 282, Issue 2, 1445-1455, January 12, 2007
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SR-BI Undergoes Cholesterol-stimulated Transcytosis to the Bile Canaliculus in Polarized WIF-B Cells*Formula

Christopher J. Harder, Andrew Meng, Peter Rippstein, Heidi M. McBride, and Ruth McPherson1

From the Lipoprotein and Atherosclerosis Group, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada

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.


Received for publication, May 15, 2006 , and in revised form, October 20, 2006.

* This work was supported by Canadian Institutes of Health Research Grants 44360 (to R. M.) and 43935 (to H. M. M.) and by an Ontario Graduate Scholarship in Science and Technology (to C. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Formula The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1-3 and Movies 1-4.

1 To whom correspondence should be addressed: Lipoprotein and Atherosclerosis Group, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada. Tel.: 613-761-5256; Fax: 613-761-5281; E-mail: rmcpherson{at}ottawaheart.ca.


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