Pre-equilibrium sensing and signaling

ALEJANDRA C VENTURA

Buenos Aires

Workshop; First Systems Biology Workshop at the School of Exact and Natural Sciences; 2014

Cell signaling systems sense andrespond to ligands that bind cell surface receptors. These systems oftenrespond to changes in the concentration of extracellular ligand that occur morerapidly than the ligand equilibrates with its receptor. We demonstrate, bymodeling and experiment, a general, "systems level" mechanism cellsuse to take advantage of the information present in the early signal, beforereceptor binding reaches a new steady state. This mechanism, PRESS, for PReEquilibrium Sensing and Signaling, operates in signaling systems in which thekinetics of ligand receptor binding are slower than the downstream signalingsteps, and typically involves transient activation of a downstream step. Insystems where it operates, PRESS expands and shifts the input dynamic range,allowing cells to make different responses to ligand concentrations so high asto be otherwise indistinguishable. Specifically, we show that PRESS applies tothe yeast directional polarization in response to pheromone gradients.Consideration of pre-existing kinetic data for receptor ligand interactionssuggests that PRESS operates in many cell signaling systems throughout biology.The same mechanism may also operate at other levels in signaling systems inwhich a slow activation step couples to a faster downstream step.