The variable cell, signal transduction at the single cell level

ALEJANDRO COLMAN LERNER; ANDREW GORDON; GUSTAVO PESCE; ROGER BRENT

Okinawa Institute of Science and Technology, Okinawa, Japón

Workshop; Systems biology of MAP kinase pathways in S.cereveisiae and in mammalian cells; 2008

Okinawa Institute of Science and Technology

We studied the quantitative behavior and cell-to-cell variability of a prototypical eukaryotic cell fate decision system, the mating pheromone response pathway in yeast. We dissected and measured sources of variation in system output analyzing thousands of individual, genetically identical cells.  Only a small portion of total cell-to-cell variation was caused by random fluctuations in gene transcription and translation during the response ("expression noise"). Instead, variation was dominated by differences in the capacity of individual cells to transmit signals through the pathway ("pathway capacity") and to express genes into proteins ("expression capacity").  Cells with high expression capacity expressed genes at a higher rate and increased in volume more rapidly. In addition, our results revealed two mechanisms that regulated cell-to-cell variation in pathway capacity. First, the pathway MAP kinase Fus3 suppressed variation at high pheromone while the MAP kinase Kss1 enhanced variation at low doses. Second, pathway and expression capacity were negatively correlated, suggesting a compensatory mechanism that allowed cells to respond more precisely to pheromone in the presence of a large variation in expression capacity.