Insulin-stimulated plasma membrane fusion of Glut4 glucose transporter-containing vesicles is regulated by phospholipase D1
Insulin-stimulated plasma membrane fusion of Glut4 glucose transporter-containing vesicles is regulated by phospholipase D1
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DOI：
10.1091/mbc.e04-12-1124
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发表时间：
2005-06-01
影响因子：
3.3
通讯作者：
Frohman, MA
中科院分区：
文献类型：
--
作者：
Huang, P;Altshuller, YM;Frohman, MA
胰岛素通过动员GLUT4葡萄糖转运体从细胞内膜储存部位到质膜来刺激脂肪和肌肉对葡萄糖的摄取。这一过程需要将含有GLUT4的囊泡运输到细胞外围，停靠在胞外部位，并进行质膜融合。我们在这里表明，磷脂酶D(PLD)的产生是融合过程中的一个关键事件。PLD1存在于含有GLUT4的囊泡上，被胰岛素信号激活，并与GLUT4一起运输到胞外部位。PLD1活性的增加有利于葡萄糖的摄取，而PLD1活性的降低则是抑制作用。PA产生的减少不会实质上阻碍囊泡的运输或它们在质膜上的停靠，但它确实会阻碍融合介导的转运蛋白的细胞外暴露。由RNA干扰介导的PLD1缺陷引起的融合障碍可以通过外源提供促进融合孔形成和扩张的脂类来挽救，这表明PA调控的步骤在囊泡融合过程中较晚。
Insulin stimulates glucose uptake in fat and muscle by mobilizing Glut4 glucose transporters from intracellular membrane storage sites to the plasma membrane. This process requires the trafficking of Glut4-containing vesicles toward the cell periphery, docking at exocytic sites, and plasma membrane fusion. We show here that phospholipase D (PLD) production of the lipid phosphatidic acid (PA) is a key event in the fusion process. PLD1 is found on Glut4-containing vesicles, is activated by insulin signaling, and traffics with Glut4 to exocytic sites. Increasing PLD1 activity facilitates glucose uptake, whereas decreasing PLD1 activity is inhibitory. Diminished PA production does not substantially hinder trafficking of the vesicles or their docking at the plasma membrane, but it does impede fusion-mediated extracellular exposure of the transporter. The fusion block caused by RNA interference-mediated PLD1 deficiency is rescued by exogenous provision of a lipid that promotes fusion pore formation and expansion, suggesting that the step regulated by PA is late in the process of vesicle fusion.