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

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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.