Volume 22, No 8, Aug 2012

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 22 Issue 8, August 2012: 1246-1257

ORIGINAL ARTICLES

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

Hui-Ling Guo^1,*, Cixiong Zhang^1,*, Qi Liu^1,*, Qinxi Li¹, Guili Lian¹, Di Wu¹, Xuebin Li¹, Wei Zhang¹, Yuemao Shen^1,2, Zhiyun Ye¹, Shu-Yong L

¹State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, China
²State Key Laboratory of Microbial Technology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China Correspondence: Sheng-Cai Lin,(linsc@xmu.edu.cn)

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 translocation 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-Golgi 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 translocation.

Cell Research (2012) 22:1246-1257. doi:10.1038/cr.2012.52; published online 3 April 2012

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