Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes
Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes
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DOI：
10.1074/jbc.272.28.17551
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发表时间：
1997-07-11
影响因子：
4.8
通讯作者：
Quehenberger, O
中科院分区：
文献类型：
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作者：
Murao, K;Terpstra, V;Quehenberger, O
最近，鉴定出一种小鼠 B 型 I 型清道夫受体 (SR-BI)，它与高密度脂蛋白 (HDL) 结合并介导胆固醇酯的选择性摄取。条形 D36 下的人类 (C) 和条形 IMPII 下的 (L) Nalogous-1 (CLA-1) 受体与 SR-BI 表现出高度的序列同源性，但其功能关系尚未确定。表达 CLA-1 的转染细胞与K-d约为35μg/ml，类似于HDL与啮齿动物SR-BI结合的K-d。这种结合导致 HDL 衍生的 [H-3] 胆固醇酯在细胞内积累，而 I-125-载脂蛋白没有内化或降解。 CLA-1 在肾上腺中强烈表达，在肝脏和睾丸中也大量表达，表明 CLA-I 与 SR-BI 一样，可以在 HDL 代谢中发挥作用。然而，CLA-1 也在单核细胞中表达，并且与 SR-BI 一样，识别低密度脂蛋白的修饰形式以及天然 LDL 和阴离子磷脂。这些发现表明CLA-1可能具有额外的生理功能，我们发现CLA-1识别凋亡的胸腺细胞。我们的结果表明，CLA-1 是 SR-BI 的紧密结构同源物，在功能上也与 SR-BI 相关，并且可能作为 HDL 的“对接受体”在选择性摄取胆固醇酯方面发挥重要作用。这些研究表明，CLA-1 在识别受损细胞方面还发挥着重要作用。
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.