Scavenger receptor class B type I-mediated cholesteryl ester-selective uptake and efflux of unesterified cholesterol. Influence of high density lipoprotein size and structure.
Scavenger receptor (SR)-BI catalyzes the selective uptake of cholesteryl ester (CE) from high density lipoprotein (HDL) by a two-step process that involves the following: 1) binding of HDL to the receptor and 2) diffusion of the CE molecules into the cell plasma membrane. We examined the effects of the size of discoidal HDL particles containing wild-type (WT) apoA-I on selective uptake of CE and efflux of cellular free (unesterified) cholesterol (FC) from COS-7 cells expressing SR-BI to determine the following: 1) the influence of apoA-I conformation on the lipid transfer process, and 2) the contribution of receptor binding-dependent processes to the overall efflux of cellular FC. Large (10 nm diameter) reconstituted HDL bound to SR-BI better (B(max) approximately 420 versus 220 ng of apoA-I/mg cell protein), delivered more CE, and promoted more FC efflux than small ( approximately 8 nm) particles. When normalized to the number of reconstituted HDL particles bound to the receptor, the efficiencies of either CE uptake or FC efflux with these particles were the same indicating that altering the conformation of WT apoA-I modulates binding to the receptor (step 1) but does not change the efficiency of the subsequent lipid transfer (step 2); this implies that binding induces an optimal alignment of the WT apoA-I.SR-BI complex so that the efficiency of lipid transfer is always the same. FC efflux to HDL is affected both by binding of HDL to SR-BI and by the ability of the receptor to perturb the packing of FC molecules in the cell plasma membrane.
Thuahnai
Stephen T
ST
Division of GI/Nutrition, Lipid Research Group, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4318, USA.
Lund-Katz
Sissel
S
Dhanasekaran
Padmaja
P
de la Llera-Moya
Margarita
M
Connelly
Margery A
MA
Williams
David L
DL
Rothblat
George H
GH
Phillips
Michael C
MC
D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation
D002788:Cholesterol Esters; D018076:DNA, Complementary; D008055:Lipids; D008075:Lipoproteins, HDL; D002784:Cholesterol