ENERGY ME TABOL I SM MODULAT E S THE PHEROMONE RESPONSE GPCR PATHWAY IN THE YEAST S.cerevisiae

ALICIA GRANDE; KENNEDY E; RODRIGO BALTANÁS; ALEJANDRO COLMAN LERNER

Argentina

Congreso; SAIB 46th Annual Meeting Argentine Society for Biochemistry and Molecular Biology XLVI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2010

Society for Biochemistry and Molecular Biology XLVI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Oscillatory mechanisms control aspects as diverse as seasonal breeding, circadian rhythms and early embryogenesis. Mating pheromone in yeast activates a conserved GPCR-MAPK cascade pathway. In high pheromone, yeast form a mating projection (shmoo) to fuse with a partner. If no mating occurs, cells abandon that shmoo and “search” in another direction, making a new shmoo every 100 minutes. The oscillatory mechanism underlying this searching behavior is unknown. Here we screened, by microscopy, the complete deletion collection of non-essential kinases and phosphatases to find mutants that form less shmoos. We selected 29 out of the 130 strains. These mutants grouped in different classes. Interestingly, one class included 3 enzymes that regulate PDA1, the catalytic subunit of the pyruvate dehydrogenase complex, suggesting that respiration might modulate shmoo formation. Given that yeast exhibit metabolic oscillations with a period of about 50 minutes, we hypothesize that the oscillations propagate, perhaps via ethanol levels, to the pheromone response pathway. Supporting this idea, decoupling pheromone signaling from respiration by addition of ethanol (the end product of yeast fermentation) or deletion of PDA1, greatly inhibited formation of multiple shmoos. We speculate that integration of signaling with the core metabolism might be a general strategy to elicit complex behaviors.