Abstract #23

Fus3 activity dynamics control periodic gene expression and morphogenesis. Zoe Hilioti¹, Walid Sabbagh, Jr.², Saurabh Paliwal¹, Adriel Bergmann¹, Marcus Goncalves¹, Lee Bardwell^2,3, Andre Levchenko¹. 1) Biomedical Engineering, Johns Hopkins University, Baltimore, MD; 2) Developmental and Cell Biology, University of California, Irvine, CA; 3) Institute for Genomics and Bioinformatics, University of California, Irvine, CA.
   Yeast cells have the dynamic ability to coordinate their behavior in response to extracellular cues. Exposure to mating pheromone stimulus activates the MAP kinase Fus3 signaling pathway that drives mating-specific gene expression and morphology changes such as arrest in the G1 phase of the cell cycle and polarized growth towards the source of the stimulus. Yeast cells exposed to spatially uniform levels of the pheromone, as it can naturally occur in dense cell groupings, initiate mating projections periodically as they probe for mating partner. To understand how persistent MAPK signaling coordinates periodic morphology changes in the absence of a gradient, we studied the protein dynamics of mating-specific regulators and correlated their spatial and temporal expression to data gathered from time-lapse microscopy. We exposed synchronous populations of cells to varying levels of pheromone and analyzed time-courses for the signaling activity (Fus3 activity and targeted gene expression profiles) as well as protein localization profiles of key regulatory proteins in the same experimental material. This systems biology approach coupled with computational modeling enabled us to identify unique organization properties of the MAPK network. Genetic and chemical pertubations unraveled feedback systems that are crucial in controlling the MAPK signaling and result in aberrant mating response and morphology. Based on our data, periodic projection formation is controlled by complex and tightly regulated activity of Fus3 protein that drives cytoskeletal rearrangements.

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