HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 14, 14372-14381, April 2, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/14/14372    most recent M313793200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Eckhardt, E. R. M. Articles by van der Westhuyzen, D. R. Search for Related Content PubMed PubMed Citation Articles by Eckhardt, E. R. M. Articles by van der Westhuyzen, D. R. Social Bookmarking                      What's this?

High Density Lipoprotein Uptake by Scavenger Receptor SR-BII^*

Erik R. M. Eckhardt, Lei Cai, Bing Sun, Nancy R. Webb, and Deneys R. van der Westhuyzen

From the Department of Internal Medicine, University of Kentucky and the Department of Veterans Affairs Medical Center, Lexington, Kentucky 40536

Scavenger receptor class B, type I (SR-BI) mediates selective uptake of high density lipoprotein (HDL) lipids. It is unclear whether this process occurs at the cell membrane or via endocytosis. Our group previously identified an alternative mRNA splicing variant of SR-BI, named SR-BII, with an entirely different, yet highly conserved cytoplasmic C terminus. In this study we aimed to compare HDL uptake by both isoforms. Whereas SR-BI was mainly (70%) localized on the surface of transfected Chinese hamster ovary cells, as determined by biotinylation, HDL binding at 4 °C, and studies of enhanced green fluorescent protein-tagged SR-BI/II fusion proteins, the majority of SR-BII (80-90%) was expressed intracellularly. The cellular distribution of SR-BI was not affected by deletion of the C terminus, which suggests that the distinct C terminus of SR-BII is responsible for its intracellular expression. Pulse-chase experiments showed that SR-BII rapidly internalized HDL protein, whereas in the case of SR-BI most HDL protein remained surface bound. Like its ligand, SR-BII was more rapidly endocytosed compared with SR-BI. Despite more rapid HDL uptake by SR-BII than SR-BI, selective cholesteryl ether uptake was significantly lower. Relative to their levels of expression at the cell surface, however, both isoforms mediated selective uptake with similar efficiency. HDL protein that was internalized by SR-BII largely co-localized with transferrin in the endosomal recycling compartment. Within the endosomal recycling compartment of SR-BII cells, there was extensive co-localization of internalized HDL lipid and protein. These results do not support a model that selective lipid uptake by SR-BI requires receptor/ligand recycling within the cell. We conclude that SR-BII may influence cellular cholesterol trafficking and homeostasis in a manner that is distinct from SR-BI.

Received for publication, December 17, 2003 , and in revised form, January 14, 2004.

^* This work was supported by American Heart Association Grants 0225289B (to E. R. M. E.) and 013002ON (to N. R. W.) and by National Institutes of Health Grant HL63763 (to D. R. V.). 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.

To whom correspondence should be addressed: University of Kentucky Medical Center MN 520, 800 Rose St., Lexington, KY 40536-0298. Tel.: 859-233-4511 (ext. 4580); Fax: 859-323-5707; E-mail: dvwest1{at}uky.edu.

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

This article has been cited by other articles:

				S. A. Fenske, A. Yesilaltay, R. Pal, K. Daniels, A. Rigotti, M. Krieger, and O. Kocher Overexpression of the PDZ1 Domain of PDZK1 Blocks the Activity of Hepatic Scavenger Receptor, Class B, Type I by Altering Its Abundance and Cellular Localization J. Biol. Chem., August 8, 2008; 283(32): 22097 - 22104. [Abstract] [Full Text] [PDF]

				X. Zhang, A. N. Moor, K. A. Merkler, Q. Liu, and M. P. McLean Regulation of Alternative Splicing of Liver Scavenger Receptor Class B Gene by Estrogen and the Involved Regulatory Splicing Factors Endocrinology, November 1, 2007; 148(11): 5295 - 5304. [Abstract] [Full Text] [PDF]

				J. Grove, T. Huby, Z. Stamataki, T. Vanwolleghem, P. Meuleman, M. Farquhar, A. Schwarz, M. Moreau, J. S. Owen, G. Leroux-Roels, et al. Scavenger Receptor BI and BII Expression Levels Modulate Hepatitis C Virus Infectivity J. Virol., April 1, 2007; 81(7): 3162 - 3169. [Abstract] [Full Text] [PDF]

				Y. Zhang, A. M. Ahmed, N. McFarlane, C. Capone, D. R. Boreham, R. Truant, S. A. Igdoura, and B. L. Trigatti Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathways J. Lipid Res., February 1, 2007; 48(2): 405 - 416. [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]

				C. D. Akpovi, S. R. Yoon, M. L. Vitale, and R-M. Pelletier The predominance of one of the SR-BI isoforms is associated with increased esterified cholesterol levels not apoptosis in mink testis J. Lipid Res., October 1, 2006; 47(10): 2233 - 2247. [Abstract] [Full Text] [PDF]

				S. Shetty, E. R.M. Eckhardt, S. R. Post, and D. R. van der Westhuyzen Phosphatidylinositol-3-Kinase Regulates Scavenger Receptor Class B Type I Subcellular Localization and Selective Lipid Uptake in Hepatocytes Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 2125 - 2131. [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]

				T. A. Pagler, S. Rhode, A. Neuhofer, H. Laggner, W. Strobl, C. Hinterndorfer, I. Volf, M. Pavelka, E. R. M. Eckhardt, D. R. van der Westhuyzen, et al. SR-BI-mediated High Density Lipoprotein (HDL) Endocytosis Leads to HDL Resecretion Facilitating Cholesterol Efflux J. Biol. Chem., April 21, 2006; 281(16): 11193 - 11204. [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]

				E. R. M. Eckhardt, L. Cai, S. Shetty, Z. Zhao, A. Szanto, N. R. Webb, and D. R. Van der Westhuyzen High Density Lipoprotein Endocytosis by Scavenger Receptor SR-BII Is Clathrin-dependent and Requires a Carboxyl-terminal Dileucine Motif J. Biol. Chem., February 17, 2006; 281(7): 4348 - 4353. [Abstract] [Full Text] [PDF]

				X.-A. Li, L. Guo, J. L. Dressman, R. Asmis, and E. J. Smart A Novel Ligand-independent Apoptotic Pathway Induced by Scavenger Receptor Class B, Type I and Suppressed by Endothelial Nitric-oxide Synthase and High Density Lipoprotein J. Biol. Chem., May 13, 2005; 280(19): 19087 - 19096. [Abstract] [Full Text] [PDF]

				L. Cai, M. C. de Beer, F. C. de Beer, and D. R. van der Westhuyzen Serum Amyloid A Is a Ligand for Scavenger Receptor Class B Type I and Inhibits High Density Lipoprotein Binding and Selective Lipid Uptake J. Biol. Chem., January 28, 2005; 280(4): 2954 - 2961. [Abstract] [Full Text] [PDF]