Role of importin-alpha in the regulation of glucose-responsive gene expression

葡萄糖是包括人类在内的大多数动物细胞的首选营养物质。为了适应营养供应的变化，葡萄糖的可用性必须在细胞膜上被感知，并迅速传递到含有排列在染色体上的基因的细胞核。一旦信号到达细胞核，一组独特的基因就被转录，最终导致蛋白质的产生，促进葡萄糖的适当吸收和代谢。这一信号依赖于位于质膜上的葡萄糖载体和细胞核中称为转录调节因子的蛋白质的功能。转录调节器确保适当的基因激活，从而将营养供应与新陈代谢联系起来。我们建议在分子水平上定义连接细胞外葡萄糖检测和葡萄糖调节基因激活的信号事件，这些反应尚未完全理解。在细胞成像、质谱学和基因表达分析中使用最先进的方法，我们期待我们的研究将为基础生物反应提供新的见解。这些过程对细胞、器官和生物体在正常和大量病理条件下的生理至关重要，包括糖尿病和肥胖症。

Glucose is the preferred nutrient for most animal cells, including man. To adapt to changes in nutrient supply, the availability of glucose has to be sensed at the cell membrane and rapidly communicated to the nucleus, which contains the genes arrayed on chromosomes. Once the signal has reached the nucleus, a unique set of genes is transcribed, ultimately leading to the production of proteins that promote proper uptake and metabolism of glucose. This signaling depends on the function of glucose carriers located at the plasma membrane and proteins in the nucleus called transcriptional regulators. The transcriptional regulators ensure proper gene activation, thereby connecting nutrient supply to metabolism. We propose to define at the molecular level the signaling events that connect the detection of extracellular glucose and the activation of glucose-regulated genes, reactions that are not completely understood. Using state-of-the-art methods in cell imaging, mass spectrometry and gene expression analysis we expect that our research will provide new insights into fundamental biological reactions. These processes are crucial to the physiology of cells, organs and organisms under normal and a large number of pathological conditions, including diabetes and obesity.