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Journal of Lipid Research, Vol. 45, 513-528, March 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Dimerization of the scavenger receptor class B type I

Eve Reaven^1,*, Yuan Cortez^*, Susan Leers-Sucheta^*, Ann Nomoto^* and Salman Azhar^*,

^* Geriatrics Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA
Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA

¹ To whom correspondence should be addressed. e-mail: eve.reaven{at}med.va.gov

This study has examined the dimeric/oligomeric forms of scavenger receptor class B type I (SR-BI) and its alternatively spliced form, SR-BII, in a diverse group of cells and tissues: i.e., normal and hormonally altered tissues of mice and rats as well as tissues of transgenic animals and genetically altered steroidogenic and nonsteroidogenic cells overexpressing the SR-B proteins. Using both biochemical and morphological techniques, we have seen that these dimeric and higher order oligomeric forms of SR-BI expression are strongly associated with both functional and morphological expression of the selective HDL cholesteryl ester uptake pathway. Rats and mice show some species differences in expression of SR-BII dimeric forms; this difference does not extend to the use of SR-B cDNA types for transfection purposes. In a separate study, cotransfection of HEK293 cells with cMyc and V5 epitope-tagged SR-BI permitted coprecipitation and quantitative coimmunocytochemical measurements at the electron microscope level, suggesting that much of the newly expressed SR-BI protein in stimulated cells dimerizes and that the SR-BI dimers are localized to the cell surface and specifically to microvillar or double membraned intracellular channels.

These combined data suggest that SR-BI self-association represents an integral step in the selective cholesteryl ester uptake process.

Supplementary key words selective pathway • cholesterol uptake • high density lipoprotein cholesteryl ester delivery

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