title: Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I.
abstract: The scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters from high-density lipoprotein (HDL) and cholesterol secretion into bile in the liver. In this study, we identified an SR-BI-associated protein from rat liver membrane extracts by using an affinity chromatography technique. This protein of 523 amino acids contains four PDZ domains and associates with the C terminus of SR-BI by using its N-terminal first PDZ domain. Therefore, we denoted this protein as CLAMP (C-terminal linking and modulating protein). CLAMP was located mostly in the sinusoidal membranes, whereas SR-BI was detected in both sinusoidal and canalicular membranes. After the solubilization of the liver membranes with Triton X-100, SR-BI was immunoprecipitated with anti-CLAMP monoclonal antibody, suggesting the association of these proteins in vivo. By coexpressing SR-BI with CLAMP in Chinese hamster ovary cells, we observed (i) the increase in the expression level of SR-BI, (ii) the reduction in the deacylation rate of the cholesteryl esters taken up from HDL, and (iii) the change in the intracellular distribution of fluorescent lipid 1,1'-dioctadecyl-3,3, 3',3'-tetramethylindocarbocyanine percholate taken up from HDL. Taken together, these data suggest that CLAMP, a four-PDZ-domain-containing protein, is associated with SR-BI in the liver sinusoidal plasma membranes and may modulate the intracellular transport and metabolism of cholesteryl esters taken up from HDL.
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ikemoto
authors.forename: H
authors.initials: H
authors.lastname: Arai
authors.forename: D
authors.initials: D
authors.lastname: Feng
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: J
authors.initials: J
authors.lastname: Aoki
authors.forename: N
authors.initials: N
authors.lastname: Dohmae
authors.forename: K
authors.initials: K
authors.lastname: Takio
authors.forename: H
authors.initials: H
authors.lastname: Adachi
authors.forename: M
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: K
authors.initials: K
authors.lastname: Inoue
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018955:CD36 Antigens; D016466:CHO Cells; D002788:Cholesterol Esters / Q000378:metabolism; D006224:Cricetinae; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000737:chemistry; D008297:Male; D008565:Membrane Proteins / Q000302:isolation & purification* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000302:isolation & purification / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
chemical_list: D018955:CD36 Antigens; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B