دورية أكاديمية
The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation
| العنوان: | The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation |
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| المؤلفون: | Guo, Hui-Ling, Zhang, Cixiong, Liu, Qi, Li, Qinxi, Lian, Guili, Wu, Di, Li, Xuebin, Zhang, Wei, Shen, Yuemao, Ye, Zhiyun, Lin, Shu-Yong, 林舒勇, Lin, Sheng-Cai, 林圣彩 |
| بيانات النشر: | INST BIOCHEMISTRY & CELL BIOLOGY |
| سنة النشر: | 2012 |
| المجموعة: | Xiamen University Institutional Repository |
| مصطلحات موضوعية: | Axin, TNKS, KIF3A, GLUT4 translocation |
| الوصف: | 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. ; National Basic Research Program of China [2011CB910800]; National Natural Science Foundation of China [31130016, 30921005, 30970613, NCET-09-0675]; Science Planning Program of Fujian Province [2009J06021] |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1001-0602 |
| العلاقة: | CELL RESEARCH，2012,22（8）：1246-1257; WOS:000307119500009; http://dx.doi.org/10.1038/cr.2012.52Test; http://dspace.xmu.edu.cn/handle/2288/15025Test |
| DOI: | 10.1038/cr.2012.52 |
| الإتاحة: | https://doi.org/10.1038/cr.2012.52Test http://dspace.xmu.edu.cn/handle/2288/15025Test |
| رقم الانضمام: | edsbas.84AA8AD5 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 10010602 |
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| DOI: | 10.1038/cr.2012.52 |