Dimerization of the scavenger receptor class B type I: formation, function, and localization in diverse cells and tissues.
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.
Reaven
Eve
E
Geriatrics Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, USA. eve.reaven@med.va.gov
Cortez
Yuan
Y
Leers-Sucheta
Susan
S
Nomoto
Ann
A
Azhar
Salman
S
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D019281:Dimerization; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D051907:Lysosomal Membrane Proteins; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010053:Ovary / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000737:chemistry / Q000378:metabolism; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012795:Sialoglycoproteins
D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D012795:Sialoglycoproteins