CLA-1 Is an 85-kD Plasma Membrane Glycoprotein That Acts as a High-Affinity Receptor for Both Native (HDL, LDL, and VLDL) and Modified (OxLDL and AcLDL) Lipoproteins

Calvo, Dominica; Gómez-Coronado, Diego; Lasunción, Miguel A.; Vega, Miguel A.

doi:10.1161/01.atv.17.11.2341

Cited by 216 publications

(175 citation statements)

References 47 publications

Supporting

Mentioning

165

Contrasting

Unclassified

Order By: Relevance

“…In this regard it is noteworthy that high affinity binding of HDL to a surface receptor called CD36, which in many ways resembles SR-BI (41), is not sufficient to ensure efficient cellular selective lipid uptake or unesterified cholesterol efflux. Thus, CD36, which shares many structural and functional similarities to SR-BI (41), was initially shown to bind HDL tightly (22,25) but not mediate efficient selective lipid uptake (25). These findings were independently confirmed (62) and extended by the analysis of cholesterol efflux (48).…”

Section: Effects Of Apoa-i Mutations On Binding and Cholesterol Efflumentioning

confidence: 96%

“…SR-BI binds HDL and rHDL, at least in part via apoA-I (14,15). In addition, it can bind other lipoproteins (21,22) and exhibits complex binding properties consistent with multiple classes of binding sites or modes of binding different ligands (19,23,24). On binding lipoproteins, SR-BI mediates both selective cholesteryl ester uptake from the lipoprotein to the cells (19,(23)(24)(25) and bi-directional unesterified cholesterol movement (23,26,27).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Effects of Mutations in Helices 4 and 6 of ApoA-I on Scavenger Receptor Class B Type I (SR-BI)-mediated Cholesterol Efflux Suggest That Formation of a Productive Complex between Reconstituted High Density Lipoprotein and SR-BI Is Required for Efficient Lipid Transport

Liu¹,

Krieger²,

Kan³

et al. 2002

Journal of Biological Chemistry

120

View full text Add to dashboard Cite

We have studied the effects of mutations in apoA-I on reconstituted high density lipoprotein (HDL) particle (rHDL(apoA-I)) binding to and cholesterol efflux from wild-type (WT) and mutant forms of the HDL receptor SR-BI expressed by ldlA-7 cells. Mutations in helix 4 or helix 6 of the apoA-I reduced efflux by 79 and 51%, respectively, without substantially altering receptor binding (apparent K d values of 1.1-4.4 g of protein/ml). SR-BI with an M158R mutation bound poorly to rHDL with WT and helix 4 mutant apoA-I; the helix 6 mutant restored tight binding to SR-BI(M158R) (K d values of 48, 60, and 7 g of protein/ml, respectively). SR-BI(M158R)-mediated cholesterol efflux rates, normalized for binding, were high for all three rHDLs (71-111% of control). In contrast, absolute (12-19%) and binding-corrected (24 -47%) efflux rates for all three rHDLs mediated by SR-BI with Q402R/Q418R mutations were very low. We propose that formation of a productive complex between apoA-I in rHDL and SR-BI, in which the lipoprotein and the receptor must either be precisely aligned or have the capacity to undergo appropriate conformational changes, is required for efficient SR-BI-mediated cholesterol efflux. Some mutations in apoA-I and/or SR-BI can result in high affinity, but non-productive, binding that does not permit efficient cholesterol efflux.

show abstract

Section: Effects Of Apoa-i Mutations On Binding and Cholesterol Efflumentioning

confidence: 96%

mentioning

confidence: 99%

The Effects of Mutations in Helices 4 and 6 of ApoA-I on Scavenger Receptor Class B Type I (SR-BI)-mediated Cholesterol Efflux Suggest That Formation of a Productive Complex between Reconstituted High Density Lipoprotein and SR-BI Is Required for Efficient Lipid Transport

Liu¹,

Krieger²,

Kan³

et al. 2002

Journal of Biological Chemistry

120

View full text Add to dashboard Cite

show abstract

“…Further studies of the human homologue demonstrated that it also is a multilipoprotein receptor that binds HDL, LDL, and VLDL. 2,10 Further analysis in vivo in mice and rats has supported a role for SR-BI in cholesterol metabolism. Targeted disruption of apoAI, the major protein component of HDL, leads to an increase in SR-BI expression in the adrenal glands of mice, 11 where HDL-C is used for steroid hormone synthesis.…”

mentioning

confidence: 99%

Association of Polymorphisms at the SR-BI Gene Locus With Plasma Lipid Levels and Body Mass Index in a White Population

Acton

Osgood

Donoghue

et al. 1999

ATVB

193

158

View full text Add to dashboard Cite

Abstract-The scavenger receptor class B type I (SR-BI) is a lipoprotein receptor that has been shown to be important in high density lipoprotein cholesterol (HDL-C) metabolism in mice. To determine its role in humans, we have characterized the human SR-BI gene and investigated its genetic variation in 489 white men and women. Five variants were demonstrated: 2 in introns (3 and 5) and 3 in exons (1, 8, and 11). Three variants at exons 1 and 8 and intron 5 with allele frequencies Ͼ0.1 were used to examine associations with lipid or anthropometric variables. The exon 1 variant was significantly (PϽ0.05) associated with increased HDL-C and lower low density lipoprotein cholesterol (LDL-C) values in men, but no associations were observed in women. The exon 8 variant was associated in women with lower LDL-C concentrations (3.05Ϯ0.98 mmol/L and 3.00Ϯ0.93 mmol/L for heterozygotes and homozygotes, respectively) compared with women homozygous for the common allele T he scavenger receptor class B type I (SR-BI) is a multilipoprotein receptor found in the liver and steroidogenic glands of both mice 1 and humans 2,3 (for a review, see Reference 4). The cDNA for human SR-BI (also known as CLA-1) was originally cloned by homology to human CD36 and rat LIMPII, which are members of a family of transmembrane proteins. 5 An independent expression cloning study identified the hamster homologue by its ability to mediate the binding of modified LDL, and it was also shown to bind native LDL. 6 Subsequently, murine SR-BI was shown to mediate the uptake of lipid, but not apoprotein, from HDL into cells, 1 a process described as selective uptake. [7][8][9] This finding established SR-BI as the first HDL transmembrane receptor to be identified and cloned. Further studies of the human homologue demonstrated that it also is a multilipoprotein receptor that binds HDL, LDL, and VLDL. 2,10 Further analysis in vivo in mice and rats has supported a role for SR-BI in cholesterol metabolism. Targeted disruption of apoAI, the major protein component of HDL, leads to an increase in SR-BI expression in the adrenal glands of mice, 11 where HDL-C is used for steroid hormone synthesis. In addition, SR-BI expression levels in the adrenal glands are increased in response to adrenocorticotropic hormone and decreased in response to dexamethasone. 12 Estrogen treatment at high doses in rats greatly reduces SR-BI expression in the liver while it increases SR-BI expression in the adrenal gland and ovarian corpus luteal cells. 13 Transient overexpression of SR-BI in the livers of mice by adenoviral infection leads to a marked reduction in plasma HDL levels and a concomitant increase in plasma LDL/IDL cholesterol levels. 14 Finally, targeted disruption of the SR-BI gene in mice leads to a significant increase in plasma HDL 15,16 and reduced selective uptake of cholesterol from HDL into the liver. 16 Thus, SR-BI has clearly been shown to be a very important player in HDL metabolism in mice. However, although mice have HDL as the major cholesterol-carrying lipopr...

show abstract

“…Many lipoprotein receptors have been characterized in eukaryotes, to date only cubilin (22) and members of the CD36 superfamily of scavenger receptors (23)(24)(25) bind native HDL (without requiring ApoE as a component). The CD36 superfamily of scavenger receptors bind and take up both native HDL and LDL as well as other polyanionic ligands, including oxidized and acetylated LDL (26).…”

mentioning

confidence: 99%

Evidence for a Trypanosoma brucei Lipoprotein Scavenger Receptor

Green

Portela

Jean

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

African trypanosomes are lipid auxotrophs that live in the bloodstream of their human and animal hosts. Trypanosomes require lipoproteins in addition to other serum components in order to multiply under axenic culture conditions. Delipidation of the lipoproteins abrogates their capacity to support trypanosome growth. Both major classes of serum lipoproteins, LDL and HDL, are primary sources of lipids, delivering cholesterol esters, cholesterol, and phospholipids to trypanosomes. We show evidence for the existence of a trypanosome lipoprotein scavenger receptor, which facilitates the endocytosis of both native and modified lipoproteins, including HDL and LDL. This lipoprotein scavenger receptor also exhibits selective lipid uptake, whereby the uptake of the lipid components of the lipoprotein exceeds that of the protein components. Trypanosome lytic factor (TLF1), an unusual HDL found in human serum that protects from infection by lysing Trypanosoma brucei brucei, is also bound and endocytosed by this lipoprotein scavenger receptor. HDL and LDL compete for the binding and uptake of TLF1 and thereby attenuate the trypanosome lysis mediated by TLF1. We also show that a mammalian scavenger receptor facilitates lipid uptake from TLF1 in a manner similar to the trypanosome scavenger receptor. Based on these results we propose that HDL, LDL, and TLF1 are all bound and taken up by a lipoprotein scavenger receptor, which may constitute the parasite's major pathway mediating the uptake of essential lipids.

show abstract

CLA-1 Is an 85-kD Plasma Membrane Glycoprotein That Acts as a High-Affinity Receptor for Both Native (HDL, LDL, and VLDL) and Modified (OxLDL and AcLDL) Lipoproteins

Cited by 216 publications

References 47 publications

The Effects of Mutations in Helices 4 and 6 of ApoA-I on Scavenger Receptor Class B Type I (SR-BI)-mediated Cholesterol Efflux Suggest That Formation of a Productive Complex between Reconstituted High Density Lipoprotein and SR-BI Is Required for Efficient Lipid Transport

The Effects of Mutations in Helices 4 and 6 of ApoA-I on Scavenger Receptor Class B Type I (SR-BI)-mediated Cholesterol Efflux Suggest That Formation of a Productive Complex between Reconstituted High Density Lipoprotein and SR-BI Is Required for Efficient Lipid Transport

Association of Polymorphisms at the SR-BI Gene Locus With Plasma Lipid Levels and Body Mass Index in a White Population

Evidence for a Trypanosoma brucei Lipoprotein Scavenger Receptor

Contact Info

Product

Resources

About