Caveolin-1 is required for fatty acid translocase (FAT/CD36) localization and function at the plasma membrane of mouse embryonic fibroblasts
Caveolin-1 is required for fatty acid translocase (FAT/CD36) localization and function at the plasma membrane of mouse embryonic fibroblasts
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DOI：
10.1016/j.bbalip.2006.03.016
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发表时间：
2006-04-01
影响因子：
4.8
通讯作者：
Stremmel, Wolfgang
中科院分区：
文献类型：
--
作者：
Ring, Axel;Le Lay, Soazig;Stremmel, Wolfgang
一些证据表明，脂筏参与细胞脂肪酸摄取并影响脂肪酸移位酶（FAT/CD 36）功能。然而，它仍然是未知的，是否caveolae，一个专门的筏型，需要这种机制。在这里，我们表明，野生型（WT）小鼠胚胎成纤维细胞（MEFs）和小窝蛋白-1敲除（KO）MEFs，这是缺乏小窝，有相当的总体表达的FAT/CD 36蛋白，但改变亚细胞FAT/CD 36的定位和功能。在WT MEFs中，FAT/CD 36与脂筏富集的去污剂抗性膜（DRM）和去污剂可溶性膜（DSM）分离，而在cav-1 KO细胞中，它仅与DSM相关。亚细胞分级显示，WT MEFs中的FAT/CD 36定位于细胞内和质膜水平，而cav-1 KO MEFs中的FAT/CD 36不存在于质膜。与WT对照相比，cav-1 KO细胞中FAT/CD 36的这种错误定位导致脂肪酸摄取减少。腺病毒在KO MEFs中表达小窝蛋白-1诱导小窝形成，将FAT/CD 36重定向至质膜并拯救脂肪酸摄取。总之，我们的数据提供的证据表明，小窝蛋白-1是必要的靶向FAT/CD 36的质膜。Caveolin-1可能通过调节FAT/CD 36的表面可用性来影响脂肪酸摄取。(c)2006 Elsevier B. V.保留所有权利。
Several lines of evidence suggest that lipid rafts are involved in cellular fatty acid uptake and influence fatty acid translocase (FAT/CD36) function. However, it remains unknown whether caveolae, a specialized raft type, are required for this mechanism. Here, we show that wild-type (WT) mouse embryonic fibroblasts (MEFs) and caveolin-1 knockout (KO) MEFs, which are devoid of caveolae, have comparable overall expression of FAT/CD36 protein but altered subcellular FAT/CD36 localization and function. In WT MEFs, FAT/CD36 was isolated with both lipid raft enriched detergent-resistant membranes (DRMs) and detergent-soluble membranes (DSMs), whereas in cav-1 KO cells it was exclusively associated with DSMs. Subcellular fractionation demonstrated that FAT/CD36 in WT MEFs was localized intracellularly and at the plasma membrane level while in cav-1 KO MEFs it was absent from the plasma membrane. This mistargeting of FAT/CD36 in cav-1 KO cells resulted in reduced fatty acid uptake compared to WT controls. Adenoviral expression of caveolin-1 in KO MEFs induced caveolae formation, redirection of FAT/CD36 to the plasma membrane and rescue of fatty acid uptake. In conclusion, our data provide evidence that caveolin-1 is necessary to target FAT/CD36 to the plasma membrane. Caveolin-1 may influence fatty acid uptake by regulating surface availability of FAT/CD36. (c) 2006 Elsevier B.V. All rights reserved.