AMPK通过磷酸化Exo70调控GLUT4转位和葡萄糖摄取

项目名称： AMPK通过磷酸化Exo70调控GLUT4转位和葡萄糖摄取

项目编号： No.31300970

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 占艳艳

作者单位： 厦门大学

项目金额： 24万元

中文摘要： AMPK在机体能量代谢过程中发挥着至关重要的作用。AMPK激活后可促进GLUT4转位至细胞膜进而加速葡萄糖摄取,但其作用机制目前研究较少。Exo70能启动GLUT4囊泡与细胞膜的栓系过程，从而促进胰岛素诱导的GLUT4转位。我们在前期研究中发现，AMPK可以与Exo70相互结合，并提高Exo70的丝氨酸磷酸化水平。氨基酸序列分析也发现，Exo70上存在保守的AMPK底物识别序列。这些结果提示，Exo70可能是AMPK的底物，并且可能介导了AMPK信号通路调控的GLUT4转位过程。因此，我们拟通过研究，明确AMPK对Exo70的直接磷酸化作用以及磷酸化的精确位点，并阐明AMPK磷酸化Exo70在GLUT4转位以及葡萄糖摄取过程中的作用及分子机制，以期对AMPK调控糖代谢的分子网络有更进一步的了解，同时也为以AMPK为靶点的糖尿病治疗提供新的理论基础。

中文关键词： AMPK；Exo70；GLUT4转位；葡萄糖摄取；磷酸化

英文摘要： AMPK pathway plays critical roles in metabolic regulation. Activation of AMPK promotes the translocation of GLUT4 to the cell membrane and increases glucose uptake, however, the underlying mechanisms are still largely unknown. Exo70 is required in insulin-induced GLUT4 translocation through starting its tethering to the cell membrane. We found that AMPK interacts with Exo70 and elevates its serine phosphorylation levels. The analysis of Exo70 amino acid sequence also reveals a consensus site for phosphorylation by AMPK. Thus, it is reasonable to expect Exo70 as a new substrate of AMPK, and to mediate GLUT4 translocation regulated by AMPK pathway. In this project, we will identify the direct phosphorylation of Exo70 by AMPK and mapping the exact phosphorylation sites, and further explore the functions and molecular mechanisms of Exo70 after phosphorylation by AMPK in GLUT4 translocation and glucose uptake. All these will enable us to know more about how AMPK regulates glucose metabolism, and also provide a new theoretical basis for the treatment of diabetes by targeting AMPK.

英文关键词： AMPK；Exo70；GLUT4 translocation；glucose uptake；phosphorylation