Le Lay Soazig, Hajduch Eric, Lindsay Margaret R, Le Lièpvre Xavier, Thiele Christoph, Ferré Pascal, Parton Robert G, Kurzchalia Teymuras, Simons Kai, Dugail Isabelle
Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Traffic. 2006 May;7(5):549-61. doi: 10.1111/j.1600-0854.2006.00406.x.
We have investigated the targeting of caveolin to lipid bodies in adipocytes that express high levels of caveolins and contain well-developed lipid droplets. We observed that the lipid droplets isolated from adipocytes of caveolin-1 knock out mice contained dramatically reduced levels of cholesterol, indicating that caveolin is required for maintaining the cholesterol content of this organelle. Analysis of caveolin distribution by cell fractionation and fluorescent light microscopy in 3T3-L1 adipocytes indicated that addition of cholesterol rapidly stimulated translocation of caveolin to lipid droplets. The cholesterol-induced trafficking of caveolins to lipid droplets was shown to be dynamin- and protein kinase C (PKC)-dependent and modulated by src tyrosine kinase activation, suggesting a role for caveolar endocytosis in this novel trafficking pathway. Consistent with this, caveolae budding was stimulated by cholesterol addition. The present data identify lipid droplets as potential target organelles for caveolar endocytosis and demonstrate a role for caveolin-1 in the maintenance of free cholesterol levels in adipocyte lipid droplets.
我们研究了窖蛋白在高表达窖蛋白且含有发育良好脂滴的脂肪细胞中向脂质体的靶向作用。我们观察到，从窖蛋白-1基因敲除小鼠的脂肪细胞中分离出的脂滴所含胆固醇水平显著降低，这表明窖蛋白是维持该细胞器胆固醇含量所必需的。通过细胞分级分离和荧光显微镜对3T3-L1脂肪细胞中窖蛋白分布的分析表明，添加胆固醇会迅速刺激窖蛋白向脂滴的转位。胆固醇诱导的窖蛋白向脂滴的运输被证明是依赖发动蛋白和蛋白激酶C（PKC）的，并受src酪氨酸激酶激活的调节，这表明小窝内吞作用在这条新的运输途径中发挥作用。与此一致的是，添加胆固醇会刺激小窝出芽。目前的数据确定脂滴是小窝内吞作用的潜在靶细胞器，并证明窖蛋白-1在维持脂肪细胞脂滴中游离胆固醇水平方面的作用。
