Choudhury Amit, Marks David L, Proctor Kirsty M, Gould Gwyn W, Pagano Richard E
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street, S.W., Rochester, MN 55905, USA.
Nat Cell Biol. 2006 Apr;8(4):317-28. doi: 10.1038/ncb1380. Epub 2006 Mar 26.
Caveolar endocytosis has an important function in the cellular uptake of some bacterial toxins, viruses and circulating proteins. However, the molecular machinery involved in regulating caveolar uptake is poorly defined. Here, we demonstrate that caveolar endocytosis is regulated by syntaxin 6, a target membrane soluble N-ethylmaleimide attachment protein receptor (t-SNARE) involved in membrane fusion events along the secretory pathway. When syntaxin 6 function was inhibited, internalization through caveolae was dramatically reduced, whereas other endocytic mechanisms were unaffected. Syntaxin 6 inhibition also reduced the presence of caveolin-1 and caveolae at the plasma membrane. In addition, syntaxin 6 inhibition decreased the delivery of GM1 ganglioside (GM1) and glycosylphosphatidylinositol (GPI)-GFP (but not vesicular stomatitis virus-glycoprotein G; VSV-G) protein from the Golgi complex to the plasma membrane. Addition of GM1 to syntaxin 6-inhibited cells resulted in the reappearance of caveolin-1 and caveolae at the plasma membrane, and restored caveolar uptake. These results suggest that syntaxin 6 regulates the delivery of microdomain-associated lipids and proteins to the cell surface, which are required for caveolar endocytosis.
小窝内吞作用在细胞摄取某些细菌毒素、病毒和循环蛋白方面具有重要功能。然而，参与调节小窝摄取的分子机制仍不清楚。在这里，我们证明小窝内吞作用受Syntaxin 6调节，Syntaxin 6是一种靶膜可溶性N-乙基马来酰亚胺附着蛋白受体（t-SNARE），参与沿分泌途径的膜融合事件。当Syntaxin 6功能受到抑制时，通过小窝的内化作用显著降低，而其他内吞机制不受影响。Syntaxin 6抑制还减少了质膜上小窝蛋白-1和小窝的存在。此外，Syntaxin 6抑制降低了GM1神经节苷脂（GM1）和糖基磷脂酰肌醇（GPI）-绿色荧光蛋白（但不是水泡性口炎病毒糖蛋白G；VSV-G）蛋白从高尔基体复合体向质膜的转运。将GM1添加到Syntaxin 6抑制的细胞中导致质膜上小窝蛋白-1和小窝重新出现，并恢复小窝摄取。这些结果表明，Syntaxin 6调节与微区相关的脂质和蛋白向细胞表面的转运，而这是小窝内吞作用所必需的。
