The class B, type I scavenger receptor promotes the selective uptake of high density lipoprotein cholesterol ethers into caveolae

Gregory A. Graf, Patrice M. Connell, Deneys R. Van Der Westhuyzen, Eric J. Smart

Research output: Contribution to journalArticlepeer-review

157 Scopus citations

Abstract

The uptake of cholesterol esters from high density lipoproteins (HDLs) is characterized by the initial movement of cholesterol esters into a reversible plasma membrane pool. Cholesterol esters are subsequently internalized to a nonreversible pool. Unlike the uptake of cholesterol from low density lipoproteins, cholesterol ester uptake from HDL does not involve the internalization and degradation of the particle and is therefore termed selective. The class B, type I scavenger receptor (SR-BI) has been identified as an HDL receptor and shown to mediate selective cholesterol ester uptake. SR-BI is localized to cholesterol- and sphingomyelin-rich microdomains called caveolae. Caveolae are directly involved in cholesterol trafficking. Therefore, we tested the hypothesis that caveolae are acceptors for HDL- derived cholesterol ether (CE). Our studies demonstrate that in Chinese hamster ovary cells expressing SR-BI, >80% of the plasma membrane associated CE is present in caveolae after 7.5 rain of selective cholesterol ether uptake. We also show that excess, unlabeled HDL can extract the radiolabeled CE from caveolae, demonstrating that caveolae constitute a reversible plasma membrane pool of CE. Furthermore, 50% of the caveolae-associated CE can be chased into a nonreversible pool. We conclude that caveolae are acceptors for HDL-derived cholesterol ethers, and that caveolae constitute a reversible, plasma membrane pool of cholesterol ethers.

Original languageEnglish
Pages (from-to)12043-12048
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number17
DOIs
StatePublished - Apr 23 1999

Funding

FundersFunder number
National Heart, Lung, and Blood Institute (NHLBI)R01HL058475
National Heart, Lung, and Blood Institute (NHLBI)

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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