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J Biol Chem, Vol. 274, Issue 1, 41-47, January 1, 1999
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From the Departments of Scavenger receptor BI (SR-BI) mediates the
selective uptake of high density lipoprotein (HDL) cholesteryl ester
(CE), a process by which HDL CE is taken into the cell without
internalization and degradation of the HDL particle. The biochemical
mechanism by which SR-BI mediates the selective uptake of HDL CE is
poorly understood. Given that CE transfer will occur to some extent
from HDL to protein-free synthetic membranes, one hypothesis is that the role of SR-BI is primarily to tether HDL close to the cell surface
to facilitate CE transfer from the particle to the plasma membrane. In
the present study, this hypothesis was tested by comparing the
selective uptake of HDL CE mediated by mouse SR-BI (mSR-BI) with that
mediated by rat CD36 (rCD36), a closely related class B scavenger
receptor. Both mSR-BI and rCD36 bind HDL with high affinity, and both
receptors mediate HDL CE selective uptake. However, SR-BI mediates
selective uptake of HDL CE with a 7-fold greater efficiency than rCD36.
HDL CE selective uptake mediated by rCD36 is dependent on HDL binding
to the receptor, since a mutation that blocks HDL binding also blocks
HDL CE selective uptake. These data lead us to hypothesize that one
component of HDL CE selective uptake is the tethering of HDL particles
to the cell surface. To explore the molecular domains responsible for the greater efficiency of selective uptake by mSR-BI, we compared binding and selective uptake among mSR-BI, scavenger receptor BII, and
various chimeric receptors formed from mSR-BI and rCD36. The results
show that the extracellular domain of mSR-BI is essential for efficient
HDL CE uptake, but the C-terminal cytoplasmic tail also has a major
influence on the selective uptake process.
Pharmacological Sciences and
¶ Physiology and Biophysics, University Medical Center, State
University at Stony Brook, Stony Brook, New York, 11794-8651 and
§ Geriatric Research, Education, and Clinical Center,
Veterans Affairs Palo Alto Health Care System,
Palo Alto, California 94304
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N. Herijgers, M. Van Eck, S. J. A. Korporaal, P. M. Hoogerbrugge, and T. J. C. Van Berkel Relative importance of the LDL receptor and scavenger receptor class B in the {beta}-VLDL-induced uptake and accumulation of cholesteryl esters by peritoneal macrophages J. Lipid Res., July 1, 2000; 41(7): 1163 - 1171. [Abstract] [Full Text]
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X. Gu, R. Lawrence, and M. Krieger Dissociation of the High Density Lipoprotein and Low Density Lipoprotein Binding Activities of Murine Scavenger Receptor Class B Type I (mSR-BI) Using Retrovirus Library-based Activity Dissection J. Biol. Chem., March 24, 2000; 275(13): 9120 - 9130. [Abstract] [Full Text] [PDF]
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Y. Ji, N. Wang, R. Ramakrishnan, E. Sehayek, D. Huszar, J. L. Breslow, and A. R. Tall Hepatic Scavenger Receptor BI Promotes Rapid Clearance of High Density Lipoprotein Free Cholesterol and Its Transport into Bile J. Biol. Chem., November 19, 1999; 274(47): 33398 - 33402. [Abstract] [Full Text] [PDF]
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S. Swarnakar, R. E. Temel, M. A. Connelly, S. Azhar, and D. L. Williams Scavenger Receptor Class B, Type I, Mediates Selective Uptake of Low Density Lipoprotein Cholesteryl Ester J. Biol. Chem., October 15, 1999; 274(42): 29733 - 29739. [Abstract] [Full Text] [PDF]
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W. V. Rodrigueza, S. T. Thuahnai, R. E. Temel, S. Lund-Katz, M. C. Phillips, and D. L. Williams Mechanism of Scavenger Receptor Class B Type I-mediated Selective Uptake of Cholesteryl Esters from High Density Lipoprotein to Adrenal Cells J. Biol. Chem., July 16, 1999; 274(29): 20344 - 20350. [Abstract] [Full Text] [PDF]
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M. Febbraio, N. A. Abumrad, D. P. Hajjar, K. Sharma, W. Cheng, S. F. A. Pearce, and R. L. Silverstein A Null Mutation in Murine CD36 Reveals an Important Role in Fatty Acid and Lipoprotein Metabolism J. Biol. Chem., July 2, 1999; 274(27): 19055 - 19062. [Abstract] [Full Text] [PDF]
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M. de la Llera-Moya, G. H. Rothblat, M. A. Connelly, G. Kellner-Weibel, S. W. Sakr, M. C. Phillips, and D. L. Williams Scavenger receptor BI (SR-BI) mediates free cholesterol flux independently of HDL tethering to the cell surface J. Lipid Res., March 1, 1999; 40(3): 575 - 580. [Abstract] [Full Text]
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D. L. Williams, M. de la Llera-Moya, S. T. Thuahnai, S. Lund-Katz, M. A. Connelly, S. Azhar, G. M. Anantharamaiah, and M. C. Phillips Binding and Cross-linking Studies Show That Scavenger Receptor BI Interacts with Multiple Sites in Apolipoprotein A-I and Identify the Class A Amphipathic alpha -Helix as a Recognition Motif J. Biol. Chem., June 16, 2000; 275(25): 18897 - 18904. [Abstract] [Full Text] [PDF]
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X. Gu, K. Kozarsky, and M. Krieger Scavenger Receptor Class B, Type I-mediated [3H]Cholesterol Efflux to High and Low Density Lipoproteins Is Dependent on Lipoprotein Binding to the Receptor J. Biol. Chem., September 22, 2000; 275(39): 29993 - 30001. [Abstract] [Full Text] [PDF]
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N. Ohgami, R. Nagai, M. Ikemoto, H. Arai, A. Kuniyasu, S. Horiuchi, and H. Nakayama CD36, a Member of the Class B Scavenger Receptor Family, as a Receptor for Advanced Glycation End Products J. Biol. Chem., January 26, 2001; 276(5): 3195 - 3202. [Abstract] [Full Text] [PDF]
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P. G. Yancey, M. de la Llera-Moya, S. Swarnakar, P. Monzo, S. M. Klein, M. A. Connelly, W. J. Johnson, D. L. Williams, and G. H. Rothblat High Density Lipoprotein Phospholipid Composition Is a Major Determinant of the Bi-directional Flux and Net Movement of Cellular Free Cholesterol Mediated by Scavenger Receptor BI J. Biol. Chem., November 17, 2000; 275(47): 36596 - 36604. [Abstract] [Full Text] [PDF]
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J. Han, A. C. Nicholson, X. Zhou, J. Feng, A. M. Gotto Jr., and D. P. Hajjar Oxidized Low Density Lipoprotein Decreases Macrophage Expression of Scavenger Receptor B-I J. Biol. Chem., May 4, 2001; 276(19): 16567 - 16572. [Abstract] [Full Text] [PDF]
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N. Ohgami, R. Nagai, A. Miyazaki, M. Ikemoto, H. Arai, S. Horiuchi, and H. Nakayama Scavenger Receptor Class B Type I-mediated Reverse Cholesterol Transport Is Inhibited by Advanced Glycation End Products J. Biol. Chem., April 13, 2001; 276(16): 13348 - 13355. [Abstract] [Full Text] [PDF]
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M. Ikemoto, H. Arai, D. Feng, K. Tanaka, J. Aoki, N. Dohmae, K. Takio, H. Adachi, M. Tsujimoto, and K. Inoue Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I PNAS, June 6, 2000; 97(12): 6538 - 6543. [Abstract] [Full Text] [PDF]
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