GLUT4 is retained by an intracellular cycle of vesicle formation and fusion with endosomes
GLUT4 is retained by an intracellular cycle of vesicle formation and fusion with endosomes
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DOI：
10.1091/mbc.e03-07-0517
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发表时间：
2004-02-01
影响因子：
3.3
通讯作者：
McGraw, TE
中科院分区：
文献类型：
--
作者：
Karylowski, O;Zeigerer, A;McGraw, TE
细胞内储存的GLUT4葡萄糖转运蛋白在胰岛素刺激下迅速转运到细胞表面。调节GLUT4的分布是维持全身葡萄糖稳态的关键。我们发现，通过动态保留/恢复机制，GLUT4被排除在脂肪细胞的质膜之外。我们的动力学研究表明，在缺乏胰岛素的情况下，含有GLUT4的囊泡不断地发芽并与核内体融合，这些GLUT4囊泡与核内体融合的可能性是与质膜融合的5倍。我们假设这种囊泡出芽和融合的细胞内周期是GLUT4保留的活性机制的一个因素。GLUT4的转运途径与furin的转运途径并没有广泛重叠，这表明furin积聚的跨高尔基网络并不是GLUT4的重要储存库。一个完整的微管细胞骨架是胰岛素刺激下募集到细胞表面所必需的，尽管它不是基础出芽/融合周期所必需的。Nocodazole对微管细胞骨架的破坏减少了胰岛素刺激下GLUT4的胞吐，这是胰岛素刺激下GLUT4向细胞表面易位减少的原因。
The intracellularly stored GLUT4 glucose transporter is rapidly translocated to the cell surface upon insulin stimulation. Regulation of GLUT4 distribution is key for the maintenance of whole body glucose homeostasis. We find that GLUT4 is excluded from the plasma membrane of adipocytes by a dynamic retention/retrieval mechanism. Our kinetic studies indicate that GLUT4-containing vesicles continually bud and fuse with endosomes in the absence of insulin and that these GLUT4 vesicles are 5 times as likely to fuse with an endosome as with the plasma membrane. We hypothesize that this intracellular cycle of vesicle budding and fusion is an element of the active mechanism by which GLUT4 is retained. The GLUT4 trafficking pathway does not extensively overlap with that of furin, indicating that the trans-Golgi network, a compartment in which furin accumulates, is not a significant storage reservoir of GLUT4. An intact microtubule cytoskeleton is required for insulin-stimulated recruitment to the cell surface, although it is not required for the basal budding/fusion cycle. Nocodazole disruption of the microtubule cytoskeleton reduces the insulin-stimulated exocytosis of GLUT4, accounting for the reduced insulin-stimulated translocation of GLUT4 to the cell surface.