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Originally published In Press as doi:10.1194/jlr.M800055-JLR200 on March 29, 2008

Papers In Press, published online ahead of print July 1, 2008
J. Lipid Res., doi:10.1194/jlr.M800055-JLR200
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Journal of Lipid Research, Vol. 49, 1569-1576, July 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Scavenger receptor class B type I localizes to a late endosomal compartment

Malika Ahras, Thet Naing and Ruth McPherson1

Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Canada K1Y 4W7

These studies were supported by a grant from the Canadian Institutes for Health Research (CIHR) (to R.M.).

Published, JLR Papers in Press, March 29, 2008.

1 To whom correspondence should be addressed. e-mail: rmcpherson{at}ottawaheart.ca

Scavenger receptor class B type I (SR-BI) has an established role in mediating the selective uptake of cholesterol from HDL in hepatocytes, steroidogenic cells, and other tissues. SR-BI is present on the plasma membrane but also localizes to stable intracellular compartments of unknown function. Using indirect immunofluorescence and subcellular fractionation, we have investigated the subcellular distribution of SR-BI. We report that red fluorescent protein-tagged mouse SR-BI (RFP-mSR-BI) colocalizes with the late endosomal and lysosomal markers, Rab7, LBPA, and Rab9. In addition, endogenous SR-BI is also found on lysosomes and colocalizes with LAMP-2 in primary hepatocytes. Furthermore, we demonstrate that the trafficking of SR-BI through these compartments is Rab7 dependent. Interestingly, filipin staining indicates accumulation of lysosomal cholesterol in SR-BI-deficient (–/–) as compared with wild-type hepatocytes. In addition to its role as a plasma membrane receptor, SR-BI may function in cholesterol trafficking from late endosomes/lysosomes.

Supplementary key words cholesterol • selective uptake • late endosomes • lysosomes • intracellular trafficking


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