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The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation

Abstract

胰岛素刺激机体对葡萄糖的吸收,主要由葡萄糖转运蛋白GLUT4介导,对机体的糖代谢平衡起着至关重要的作用,这个过程被扰乱,会导致糖尿病。但是,这个信号途径的分子组分和调节机制还很不清楚。在本文,我们阐明了Axin与多聚核糖化酶TNKS以及动力蛋白KIF3A相互作用,形成一个三元复合体,对胰岛素应答的GLUT4转运有重要作用。特异性敲低复合体各个组分的表达,减少胰岛素刺激下GLUT4向细胞膜上的转移。重要的是,TNKS2-/-小鼠的胰岛素敏感性降低,饥饿再喂食后的血糖浓度比野生型小鼠相对高。机制方面,我们发现,无胰岛素时,Axin,TNKS和KIF3A与GLUT4在高尔基体的反面膜囊有共定位。胰岛...Insulin-stimulated glucose uptake by the glucose transporter GLUT4 plays a central role in whole-body glucose homeostasis, dysregulation of which leads to type 2 diabetes. However, the molecular components and mechanisms regulating insulin-stimulated glucose uptake remain largely unclear. Here, we demonstrate that Axin interacts with the poly ADP-ribosylase TNKS and the kinesin motor protein KIF3A...学位:理学博士院系专业:生命科学学院生物医学科学系_生物化学与分子生物学学号:2172008015041

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