Centre de Recherche des Cordeliers, INSERM, U872, Paris, France.
PLoS One. 2011;6(8):e23353. doi: 10.1371/journal.pone.0023353. Epub 2011 Aug 12.
Caveolin-1 (Cav1), a structural protein required for the formation of invaginated membrane domains known as caveolae, has been implicated in cholesterol trafficking and homeostasis. Here we investigated the contribution of Cav1 to apolipoprotein A-I (apoA-I) cell surface binding and intracellular processing using mouse embryonic fibroblasts (MEFs) derived from wild type (WT) or Cav1-deficient (Cav1(-/-)) animals. We found that cells expressing Cav1 have 2.6-fold more apoA-I binding sites than Cav1(-/-) cells although these additional binding sites are not associated with detergent-free lipid rafts. Further, Cav1-mediated binding targets apoA-I for internalization and degradation and these processes are not correlated to cholesterol efflux. Despite lower apoA-I binding, cholesterol efflux from Cav1(-/-) MEFs is 1.7-fold higher than from WT MEFs. Stimulation of ABCA1 expression with an LXR agonist enhances cholesterol efflux from both WT and Cav1(-/-) cells without increasing apoA-I surface binding or affecting apoA-I processing. Our results indicate that there are at least two independent lipid binding sites for apoA-I; Cav1-mediated apoA-I surface binding and uptake is not linked to cholesterol efflux, indicating that membrane domains other than caveolae regulate ABCA1-mediated cholesterol efflux.
窖蛋白-1（Cav1）是一种结构蛋白，对于形成凹陷的膜结构域（称为小窝）是必需的，它参与胆固醇的运输和动态平衡。在这里，我们使用从野生型（WT）或窖蛋白-1 缺失（Cav1（-/-））动物中衍生的小鼠胚胎成纤维细胞（MEF）研究了 Cav1 对载脂蛋白 A-I（apoA-I）细胞表面结合和细胞内加工的贡献。我们发现，表达 Cav1 的细胞具有比 Cav1（-/-）细胞多 2.6 倍的 apoA-I 结合位点，尽管这些额外的结合位点与无去污剂脂质筏无关。此外，Cav1 介导的结合将 apoA-I 靶向内化和降解，这些过程与胆固醇流出无关。尽管 apoA-I 的结合减少，但 Cav1（-/-）MEF 中的胆固醇流出率比 WT MEF 高 1.7 倍。用 LXR 激动剂刺激 ABCA1 表达可增强 WT 和 Cav1（-/-）细胞的胆固醇流出，而不会增加 apoA-I 表面结合或影响 apoA-I 加工。我们的结果表明，apoA-I 至少有两个独立的脂质结合位点；Cav1 介导的 apoA-I 表面结合和摄取与胆固醇流出无关，表明除小窝以外的膜结构域调节 ABCA1 介导的胆固醇流出。
