Gradient sensing in the S.cerevisiae pheromone response pathway

ALEJANDRO COLMAN LERNER; ALEJANDRA VENTURA; ALAN BUSH; ARIEL CHERNOMORETZ

Punta del Este

Simposio; Yeast Systems Biology Course - Symposium; 2011

Institut Pasteur Montevideo

Cells use membrane receptors coupled to intracellular signaling cascades to respond to signaling molecules. It is commonly accepted that levels of signal that yield maximal receptor occupation cannot be distinguished from each other. Here we revisited this notion in the light of experimental observations showing that yeast cells can orient their growth in a gradient of mating pheromone that nearly saturates its receptor (Moore et al, 2008; Paliwal et al, 2007). We present a mechanism, pre-equilibrium sensing (PES), that enables cells to discriminate levels of signals that saturate receptors at equilibrium. We show that this mechanism applies to the yeast directional polarization in response to pheromone gradients. Using a quantitative model of polarization we demostrate that agreement with experimental data (Moore et al, 2008; Paliwal et al, 2007) can only be achieved in conditions in which PES is possible. Our results underscore the importance of the kinetics of receptor occupation in determining signaling outcomes.