QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online June 28, 2004
doi: 10.1242/10.1242/jcs.01182

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rhainds, D. Articles by Brissette, L. Search for Related Content PubMed PubMed Citation Articles by Rhainds, D. Articles by Brissette, L. Social Bookmarking                         What's this?

Localization and regulation of SR-BI in membrane rafts of HepG2 cells

Département des Sciences Biologiques, Université du Québec à Montréal, 1200 Saint-Alexandre, Montréal, Québec, H3B 3H5, Canada

^* Author for correspondence (e-mail: brissette.louise{at}uqam.ca)

Accepted 24 February 2004

The scavenger receptor class B, type I (SR-BI) mediates cholesteryl esters (CE) selective uptake from low density lipoprotein (LDL) and high-density lipoprotein (HDL) particles. In a number of tissues expressing caveolin, SR-BI is localized in caveolae. We show using detergent-free sucrose gradients that SR-BI is found in membrane rafts devoid of caveolin-1 in the human hepatoma HepG2 cell. Perturbation of the structure of HepG2 cell membrane rafts with cholesterol oxidase or sphingomyelinase decreased LDL-CE association due to selective uptake by 60%, while HDL₃-CE selective uptake was increased 2.3-fold by cholesterol oxidase but was not affected by sphingomyelinase. Sequestration of membrane cholesterol with filipin III decreased LDL-CE selective uptake by 25%, while it had no effect on HDL₃-CE selective uptake. Extraction of cell membrane cholesterol with ß-cyclodextrin increased LDL- and HDL₃-CE selective uptake by 1.6-fold and 3-fold, respectively. We found that CE-selective uptake from both HDL and LDL occurs by a pathway involving retro-endocytosis in HepG2 cells. An analysis of the effect of SR-BI level on the expression of critical lipid sensor and lipid binding proteins was conducted with stable transformants of HepG2 cell overexpressing SR-BI. We found that liver-type fatty acid binding protein expression level is higher in SR-BI-overexpressing cells and that caveolin-1 and sterol response element binding protein-2 levels are reduced. Thus, in this hepatic cell model, SR-BI is associated with membrane rafts devoid of caveolin and its expression affects intracellular lipid binding and lipid sensor proteins. SR-BI-dependent LDL- and HDL-CE selective uptake are affected differently by the integrity of membrane rafts, but both occur by a retroendocytic pathway in HepG2 cells.

Key words: SR-BI, Cholesterol, Rafts, Caveolae, HepG2 cell, Lipoprotein

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Van Eck, M. Hoekstra, R. Out, I. S. T. Bos, J. K. Kruijt, R. B. Hildebrand, and T. J. C. Van Berkel Scavenger receptor BI facilitates the metabolism of VLDL lipoproteins in vivo J. Lipid Res., January 1, 2008; 49(1): 136 - 146. [Abstract] [Full Text] [PDF]

				C. J. Harder, A. Meng, P. Rippstein, H. M. McBride, and R. McPherson SR-BI Undergoes Cholesterol-stimulated Transcytosis to the Bile Canaliculus in Polarized WIF-B Cells J. Biol. Chem., January 12, 2007; 282(2): 1445 - 1455. [Abstract] [Full Text] [PDF]

				S. B. Kapadia, H. Barth, T. Baumert, J. A. McKeating, and F. V. Chisari Initiation of Hepatitis C Virus Infection Is Dependent on Cholesterol and Cooperativity between CD81 and Scavenger Receptor B Type I J. Virol., January 1, 2007; 81(1): 374 - 383. [Abstract] [Full Text] [PDF]

				B. Sun, E. R. M. Eckhardt, S. Shetty, D. R. van der Westhuyzen, and N. R. Webb Quantitative analysis of SR-BI-dependent HDL retroendocytosis in hepatocytes and fibroblasts J. Lipid Res., August 1, 2006; 47(8): 1700 - 1713. [Abstract] [Full Text] [PDF]

				J. Dong, J. Liu, B. Lou, Z. Li, X. Ye, M. Wu, and X.-C. Jiang Adenovirus-mediated overexpression of sphingomyelin synthases 1 and 2 increases the atherogenic potential in mice J. Lipid Res., June 1, 2006; 47(6): 1307 - 1314. [Abstract] [Full Text] [PDF]

				C. J. Harder, G. Vassiliou, H. M. McBride, and R. McPherson Hepatic SR-BI-mediated cholesteryl ester selective uptake occurs with unaltered efficiency in the absence of cellular energy J. Lipid Res., March 1, 2006; 47(3): 492 - 503. [Abstract] [Full Text] [PDF]

				P. V. Subbaiah, L. R. Gesquiere, and K. Wang Regulation of the selective uptake of cholesteryl esters from high density lipoproteins by sphingomyelin J. Lipid Res., December 1, 2005; 46(12): 2699 - 2705. [Abstract] [Full Text] [PDF]

				A. Papanikolaou, A. Papafotika, C. Murphy, T. Papamarcaki, O. Tsolas, M. Drab, T. V. Kurzchalia, M. Kasper, and S. Christoforidis Cholesterol-dependent Lipid Assemblies Regulate the Activity of the Ecto-nucleotidase CD39 J. Biol. Chem., July 15, 2005; 280(28): 26406 - 26414. [Abstract] [Full Text] [PDF]