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

作　　者：Hui-Ling Guo Cixiong Zhang Qi Liu Qinxi Li Guili Lian Di Wu Xuebin Li Wei Zhang Yuemao Shen Zhiyun Ye Slau-Yong Lin Sheng-Cai Lin 

机构地区：[1]State Key Laboratory of Stress Cell Biology,School of Life Sciences,Xiamen University,Xiamen,Fujian 361005,China [2]StateKey Laboratory of Microbial Technology,School of Life Sciences,Shandong University,Jinan,Shandong 250100,China

出　　处：《Cell Research》2012年第8期1246-1257,共12页细胞研究（英文版）

基　　金：Acknowledgments We thank Dr Chi NW for providing the CMV2-FLAG-TNKS2 （human） construct. This work was supported by grants from the National Basic Research Program of China （2011CB910800 to SCL）, the National Natural Science Foundation of China （31130016 to SCL, 30921005 to SCL, and 30970613 to QL）, NCET-09-0675 （to QL）, and the Science Planning Program of Fujian Province （2009J06021 to QL）.

摘　　要：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 ADP-ribosylase tankyrase 2 （TNKS2） and the kinesin motor protein KIF3A, forming a ternary complex crucial for GLUT4 transiocation in response to insulin. Specific knockdown of the individual components of the complex attenuated insulin-stimulated GLUT4 translocation to the plasma membrane. Importantly, TNKS2-/- mice exhibit reduced insulin sensitivity and higher blood glucose levels when re-fed after fasting. Mechanistically, we demonstrate that in the absence of insulin, Axin, TNKS and KIF3A are co-localized with GLUT4 on the trans-Goigi network. Insulin treatment suppresses the ADP-ribosylase activity of TNKS, leading to a reduction in ADP ribosylation and ubiquitination of both Axin and TNKS, and a concurrent stabilization of the complex. Inhibition of Akt, the major effector kinase of insulin signaling, abrogates the insulin-mediated complex stabilization. We have thus elucidated a new protein complex that is directly associated with the motor protein kinesin in insulin-stimulated GLUT4 translo- cation.

关 键 词：AXIN TNKS KIF3A GLUT4 translocation 

分 类 号：Q578[生物学—生物化学] S852.65[农业科学—基础兽医学]