Activation of mating response converts the HOG pathway from a transient to a sustained response

RODRIGO BALTANÁS; ALEJANDRO COLMAN-LERNER

Gotemburgo, Suecia

Conferencia; Ninth International Conference on Systems Biology; 2008

International Society for Systems Biology/Goteborg University

Activation of mating response converts the HOG pathway from a transient to a sustained response. Rodrigo Baltanás and Alejandro Colman-Lerner*. Instituto de Fisiología, Biología Molecular y Neurociencias, UBA-CONICET y Departamento de Fisiolgía, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. * colman-lerner@fbmc.fcen.uba.ar Objective: Cells are usually exposed to multiple environmental signals, which often act together to affect cell decisions. Here we studied how budding yeast integrates information when two signaling systems are stimulated at the same time. We chose the mating pheromone response and the high osmolarity (HOG) pathways, which share several components, and measured the activity of each pathway using cells expressing specific fluorescent protein-based transcriptional reporters. Results: The fundamentally different function of these two pathways was reflected in the duration of their respective responses. In the presence of continued stimulation, the response to pheromone was sustained, showing little to no adaptation for at least three hours. On the other hand, the response to high osmolarity was transient, as the response shuts itself off after causing an increase in internal osmolite concentration that matches the increase in external osmolarity. Co-stimulation with high osmolarity and pheromone showed that cells respond to both stimuli with no apparent correlation in their level of activation in individual cells. Surprisingly, a 90 min pretreatment with pheromone changed the high osmolarity transcriptional response from transient into sustained, for at least 3 hours. We found that this change required Mpk1, the MAP kinase of the cell wall integrity pathway (CWIP), suggesting that Mpk1 modulates the high-osmolarity response during the pheromone response. In support of this interpretation, we found that activation of the CWIP by high temperature also caused sustained HOG activation. Thus, the HOG pathway seems to be able to integrate inputs from other cellular pathways. Consistent with this idea, we observed higher cell to cell variation in the transcriptional output of the HOG pathway than in that of the pheromone pathway. Conclusions: These results show how the normally transient response of a signaling pathway can be turned into a sustained response by a modulating input from another pathway. We hypothesize that the cell wall integrity pathway partly counteracts the high-osmolarity response, thereby forcing the continued activity of the Hog pathway.