"Signal anticipation in a GPCR pathway—Single cell measurements of scaffold recruitment show rapid does response alignment before receptor binding reaches equilibrium”

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

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

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.