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 (C) under bar D36 and (L) under bar IMPII (a) under bar nalogous-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 K-d of about 35 mu g/ml, similar to the K-d for HDL binding to rodent SR-BI. This binding resulted in an intracellular accumulation of HDL-derived [H-3]cholesterol esters without internalization or degradation of I-125-apolipoprotein. CLA-1 was strongly expressed in the adrenal gland and was also abundant in liver and testis, suggesting that CLA-I, 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.