Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes.
Recently, a murine scavenger receptor type B class I (SR-BI) was identified that binds high density lipoprotein (HDL) and mediates the selective uptake of cholesterol esters. The human CD36 and LIMPII analogous-1 (CLA-1) receptor shows high sequence homology with SR-BI, but their functional relationship has not been determined. Transfected cells expressing CLA-1 bound HDL with a Kd of about 35 microg/ml, similar to the Kd for HDL binding to rodent SR-BI. This binding resulted in an intracellular accumulation of HDL-derived [3H]cholesterol esters without internalization or degradation of 125I-apolipoprotein. CLA-1 was strongly expressed in the adrenal gland and was also abundant in liver and testis, suggesting that CLA-1, like SR-BI, could play a role in the metabolism of HDL. However, CLA-1 was also expressed in monocytes and, like SR-BI, recognized modified forms of low density lipoproteins as well as native LDL and anionic phospholipids. These findings suggest that CLA-1 might have additional physiological functions. We found that CLA-1 recognizes apoptotic thymocytes. Our results demonstrate that CLA-1, a close structural homologue of SR-BI, is also functionally related to SR-BI and may play an important role as a "docking receptor" for HDL in connection with selective uptake of cholesterol esters. An additional role in recognition of damaged cells is suggested by these studies.
Murao
K
K
Department of Medicine, University of California, San Diego, La Jolla, California 92093-0682, USA.
Terpstra
V
V
Green
S R
SR
Kondratenko
N
N
Steinberg
D
D
Quehenberger
O
O
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000378:metabolism*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013950:Thymus Gland / Q000166:cytology*
D018955:CD36 Antigens; D002352:Carrier Proteins; D002788:Cholesterol Esters; D008024:Ligands; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein