Single-cell imaging of membrane recruitment of signaling scaffold: fractional receptor occupancy is sensed quantitatively seconds after addition of ligand.

ALEJANDRO COLMAN LERNER; TY THOMSON; ANDREW GORDON; ALAN BUSH; PABLO BALENZUELA; RODRIGO LAJE; LUCIANA BRUNO; ARIEL CHERNOMORETZ; KIRSTEN BENJAMIN; ROGER BRENT

Long Beach, California, Estados Unidos

Congreso; The Eigth International Conference on Systems Biology; 2007

CALTECH y UC-Irvine

Cells implement precise responses to signals. We investigated in S.cerevisiae early pheromone signal propagation. Using microscope-based cytometry, we measured membrane recruitment of the scaffold protein Ste5. Ste5 is recruited in a few seconds in response to high pheromone. We found that pheromone dose information is transmitted precisely to Ste5 but that recruitment reaches plateau levels faster than pheromone:receptor complex (“signal anticipation”). Thus, the system may "measure" the rate of pheromone binding. We developed a detailed chemical reaction model describing the known biological mechanisms. This model reproduces the cells’ behavior. We are currently exploring what feature of the model is responsible for signal anticipation.