近日，国际著名杂志Cell Research在线刊登了厦门大学生科院林圣彩课题组的最新研究成果“The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation，”，文章中，研究者揭示了葡糖糖转运的最新研究成果，该文章第一作者为博士生郭慧玲。
林圣彩教授课题组研究发现，胰岛素刺激下，AXIN/TNKS/KIF3A复合体被稳定，参与调节GLUT4膜泡向细胞膜的转移，从而使脂肪细胞膜表面的葡萄糖转运蛋白GLUT4增加，促进胰岛素调解下脂肪细胞对葡萄糖的吸收。在这个复合体内，AXIN作为架构蛋白，促进TNKS与动力蛋白KIF3A的结合。
胰岛素刺激抑制TNKS的多聚ADP核糖化酶活性，由此导致TNKS及AXIN的多聚ADP核糖化修饰和泛素化修饰信号及降解作用减弱，从而稳定复合体，促进GLUT4膜泡介由动力蛋白KIF3A的转运。该研究通过对AXIN/TNKS/KIF3A复合体的分析和功能鉴定，从细胞水平解释了GLUT4响应insulin刺激引起葡萄糖转运的机理，并对传统的insulin-GLUT4通路进行了有力的进一步说明，也是对目前国际主流认识的PI3K-AKT-AS160通路的补充。
该发现将有助于我们从更加深刻的角度认识insulin调控的葡萄糖转运的全过程，并为我们最终解释糖尿病的机理，彻底治疗糖尿病提供有益的线索。（生物谷Bioon.com）
doi:10.1038/cr.2012.52
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The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation
Hui-Ling Guo1,*, Cixiong Zhang1,*, Qi Liu1,*, Qinxi Li1, Guili Lian1, Di Wu1, Xuebin Li1, Wei Zhang1, Yuemao Shen1,2, Zhiyun Ye1, Shu-Yong Lin1 and Sheng-Cai Lin1
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.
