Bases moleculares del proceso de inducción génica por glucosa.

Abstract

Sensing nutrients is a fundamental requisite for all living cells. For most eukaryotic cells glucose is a major source of energy, having significant and varied effects on cell function. Maintaining glucose homoeostasis is consequently of great importance to many organisms. Interest in identifying mechanisms by which cells sense and respond to variations in glucose concentration has increased lately. Glucose regulates genes in all cells by mechanisms which have been conserved throughout evolution. The consensus is that glucose could act on target cells either by binding to a receptor at the cell surface, or through its metabolism. The aim of this thesis is to elucidate the mechanism involved in glucose sensing in the yeast Saccharomyces cerevisiae. Yeast cells prefer glucose as carbon source and have evolved mechanisms for sensing and responding to wildly fluctuating levels of extracellular glucose. These mechanisms involve a large family of hexose transporters (HXT proteins) and the glucose transporter homologues Snf3 and Rgt2. Snf3 and Rgt2 are glucose-sensing proteins at the plasma membrane with no detectable transport activity. They sense the extracellular glucose and generate an intracellular glucose signal that triggers the induction of HXT gene expression. Expression of HXT1, a gene encoding a Saccharomyces cerevisiae low-affinity glucose transporter, is regulated by glucose availability, being activated in the presence of glucose and inhibited when the levels of the sugar are scarce. In this study we show how glucose regulate HXT1 expression, and how glucose requires at least the coordinated action of three different mechanisms of signalling: glucose signalling pathway, osmotic stress signalling (HOG pathway) and nutrient-signalling (TOR pathway) .