近日,，國際著名雜志Cell Research在線刊登了廈門大學(xué)生科院林圣彩課題組的最新研究成果“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轉(zhuǎn)運(yùn)的最新研究成果,，該文章第一作者為博士生郭慧玲。
林圣彩教授課題組研究發(fā)現(xiàn),，胰島素刺激下,，AXIN/TNKS/KIF3A復(fù)合體被穩(wěn)定，參與調(diào)節(jié)GLUT4膜泡向細(xì)胞膜的轉(zhuǎn)移,，從而使脂肪細(xì)胞膜表面的葡萄糖轉(zhuǎn)運(yùn)蛋白GLUT4增加,，促進(jìn)胰島素調(diào)解下脂肪細(xì)胞對葡萄糖的吸收,。在這個復(fù)合體內(nèi)，AXIN作為架構(gòu)蛋白,，促進(jìn)TNKS與動力蛋白KIF3A的結(jié)合,。
胰島素刺激抑制TNKS的多聚ADP核糖化酶活性，由此導(dǎo)致TNKS及AXIN的多聚ADP核糖化修飾和泛素化修飾信號及降解作用減弱,，從而穩(wěn)定復(fù)合體,，促進(jìn)GLUT4膜泡介由動力蛋白KIF3A的轉(zhuǎn)運(yùn)。該研究通過對AXIN/TNKS/KIF3A復(fù)合體的分析和功能鑒定,，從細(xì)胞水平解釋了GLUT4響應(yīng)insulin刺激引起葡萄糖轉(zhuǎn)運(yùn)的機(jī)理,，并對傳統(tǒng)的insulin-GLUT4通路進(jìn)行了有力的進(jìn)一步說明，也是對目前國際主流認(rèn)識的PI3K-AKT-AS160通路的補(bǔ)充,。
該發(fā)現(xiàn)將有助于我們從更加深刻的角度認(rèn)識insulin調(diào)控的葡萄糖轉(zhuǎn)運(yùn)的全過程,，并為我們最終解釋糖尿病的機(jī)理，徹底治療糖尿病提供有益的線索,。（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.
