Deborde Sylvie, Perret Emilie, Gravotta Diego, Deora Ami, Salvarezza Susana, Schreiner Ryan, Rodriguez-Boulan Enrique
Department of Ophthalmology, Dyson Vision Research Institute, LC-300, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Nature. 2008 Apr 10;452(7188):719-23. doi: 10.1038/nature06828.
Clathrin-coated vesicles are vehicles for intracellular trafficking in all nucleated cells, from yeasts to humans. Many studies have demonstrated their essential roles in endocytosis and cellular signalling processes at the plasma membrane. By contrast, very few of their non-endocytic trafficking roles are known, the best characterized being the transport of hydrolases from the Golgi complex to the lysosome. Here we show that clathrin is required for polarity of the basolateral plasma membrane proteins in the epithelial cell line MDCK. Clathrin knockdown depolarized most basolateral proteins, by interfering with their biosynthetic delivery and recycling, but did not affect the polarity of apical proteins. Quantitative live imaging showed that chronic and acute clathrin knockdown selectively slowed down the exit of basolateral proteins from the Golgi complex, and promoted their mis-sorting into apical carrier vesicles. Our results demonstrate a broad requirement for clathrin in basolateral protein trafficking in epithelial cells.
网格蛋白包被小泡是从酵母到人类的所有有核细胞中进行细胞内运输的载体。许多研究已经证明了它们在质膜的内吞作用和细胞信号传导过程中的重要作用。相比之下，人们对其非内吞运输作用知之甚少，其中研究最充分的是水解酶从高尔基体复合体到溶酶体的运输。在这里，我们表明网格蛋白是上皮细胞系MDCK中基底外侧质膜蛋白极性所必需的。网格蛋白敲低通过干扰其生物合成运输和循环，使大多数基底外侧蛋白去极化，但不影响顶端蛋白的极性。定量实时成像显示，慢性和急性网格蛋白敲低选择性地减缓了基底外侧蛋白从高尔基体复合体的输出，并促进它们错误分选到顶端载体小泡中。我们的结果表明上皮细胞中基底外侧蛋白运输广泛需要网格蛋白。
