Dynamic signal processing by the glucose sensing network of Saccharomyces cerevisiae
Montaño-Gutierrez, Luis Fernando
Organisms must constantly face and adapt to environmental change. Although unpredictable events may inevitably impose threats, temporally correlated changes may also provide opportunities from which an organism can profit. An evolutionarily successful microbe must collect enough information to distinguish threats from opportunities. Indeed, for nutrient transport, it is not clear how organisms distinguish one from the other. Fluctuations in nutrient levels can quickly render any transporter's capabilities obsolete. Identifying the environment's dynamic identity is therefore a highly valuable asset for a cell to elicit an accurate physiological response. Recent evidence suggests that the baker's yeast Saccharomyces cerevisiae can exert anticipatory responses to environmental shifts. Nevertheless, the mechanisms by which cells are able to incorporate information from the environment's dynamic features is not understood. A potential source of complex information processing is a highly intricate biochemical network that controls glucose transport. The understanding of this network, however, has revolved around its ability to adjust expression of 17 hexose transporter genes (HXT) to glucose levels. In this thesis, I postulate that instead the glucose sensing network is dynamically controlling the 7 major hexose transporters. By studying transporter dynamics in several scenarios, I provide substantial evidence for this hypothesis. I find that hexose transporters with similar reported affinities (Hxt2 and Hxt4) are robustly allocated to separate stages of growth for multiple initial glucose concentrations. Using single-cell studies, I show that Hxt4 expresses exclusively during glucose downshifts, in contrast with Hxt2. From multiple approaches, I demonstrate that Mig1 is mostly responsible for reporting on the time derivative of glucose, and harnessing it to differentially regulate both transporters. I also provide evidence for the roles of Rgt2 and Std1 in modulating long-term glucose repression of Hxt4. This work extends our ideas on the functionality of transport and gene regulation beyond the established steady-state models. The ability to decode environmental dynamics is likely to be present in other signaling systems and may impact a cell's decision to use fermentation - a decision which is of fundamental interest both for cancer research and for biotechnology.